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&NA;. "Ki-67." Advances in Anatomic Pathology 3, no. 6 (1996): 376. http://dx.doi.org/10.1097/00125480-199611000-00042.
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Törzsök, Péter, Péter Riesz, István Kenessey, et al. "Claudins and Ki-67." Journal of Histochemistry & Cytochemistry 59, no. 11 (2011): 1022–30. http://dx.doi.org/10.1369/0022155411424606.
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Updated classification of urothelial cell cancer differentiates low-grade and high-grade cancers, which determines potential clinical outcome. Substantial interobserver variability necessitates new biomarkers to ensure classification. Claudins’ specific expression pattern characterizes normal tissues, different tumor types, and defined grades of tumor differentiation. The aim of this study was to examine the expression pattern of claudins and proliferation marker Ki-67 in low-grade and high-grade urothelial cell cancers compared with independent control samples of non-tumorous urothelium, as well as to reveal the predictive usefulness of claudins. The expression of claudins-1, -2, -3, -4, -5, -7, and -10 and Ki-67 was studied with quantitative immunohistochemistry and real-time RT-PCR with relative quantification in 103 samples: 86 urothelial cell cancers (27 low grade, 59 high grade) and 17 non-tumorous urothelia. Results were analyzed regarding overall survival and recurrence-free period as well. High-grade tumors overall showed significantly higher claudin-4 and Ki-67 and significantly lower claudin-7 expression when compared with low-grade ones. High-grade tumors revealed significantly shorter overall survival in Kaplan-Meier analysis. Claudin-4, claudin-7, and Ki-67 might be used as potential markers to differentiate low-grade and high-grade urothelial cell cancers, thereby possibly enhancing accuracy of pathological diagnosis and adding further information to clinical outcome.
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Wang, Dan, Zhengyu Pang, Gina M. Clarke, et al. "Ki-67 Membranous Staining." Applied Immunohistochemistry & Molecular Morphology 24, no. 6 (2016): 447–52. http://dx.doi.org/10.1097/pai.0000000000000202.
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Alexandrakis, Michael G., Freda H. Passam, Despina S. Kyriakou, Konstantina Dambaki, Maria Niniraki, and Efstathios Stathopoulos. "Ki-67 Proliferation Index." American Journal of Clinical Oncology 27, no. 1 (2004): 8–13. http://dx.doi.org/10.1097/01.coc.0000045810.91816.41.
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Dey, Poulami, Ritu Sarkar, Monoj Kumar Deka, and Arindam Das. "Ki-67 Expression in Premalignant and Malignant Lesions of Gallbladder in Southern Part of Assam." International Journal of Pharmaceutical and Clinical Research 16, no. 5 (2024): 682–86. https://doi.org/10.5281/zenodo.11409388.
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<strong>Introduction:</strong> Gallbladder cancer is the most common malignancies of the biliary tract and among the gastrointestinal malignancies. Gall stones, pyloric and intestinal metaplasia have been found to be associated with gall bladder carcinoma. Ki-67 is a good marker for cell proliferation and its expression is correlated with various lesions of gall bladder. <strong>Aim:</strong> The aim of the study is to assess the ki-67 expression in different malignant and premalignant lesions of gall bladder. <strong>Materials and Methods:</strong> The retrospective study included 212 cases of gall bladder lesions, out of which 22 cases were malignant and 75 premalignant lesions. Immunohistochemistry was done for ki-67 expression. A percentage of >20% stained cells was considered to be positive regardless of the intensity of staining. <strong>Results:</strong> It was observed that out of 212 cases, 179(84%) cases were female and 33(16%) cases are males. The incidence of gall bladder lesions was highest in 41-50 years (36%) and malignant cases were highest in >50 years (55%). In the malignant groups, Ki-67 expression was <20% in 59% cases, 20-30% in 27% cases and >30% in 14% cases. Ki-67 expression was highest in moderately and well differentiated gall bladder carcinomas than poorly differentiated carcinomas. <strong>Conclusion:</strong> Ki-67 can be used as a good marker of aggression of various lesions of gall bladder.
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Kaur, Ravneet, Parul Gupta, Vandana Agarwal, and Anee Mathur. "KI-67 LABELLING INDEX IN UROTHELIAL NEOPLASM." Era's Journal of Medical Research 10, no. 01 (2023): 13–18. http://dx.doi.org/10.24041/ejmr2023.2.
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Urothelial neoplasms can be classified as non-invasive & invasive lesions. The major prognostic factors are degree of differentiation and depth of invasion in urothelial tumors. Ki-67 is a non- histone nuclear protein marker of cell proliferation which is encoded by MKi-67 gene in humans. This study evaluates and correlate immunohistochemical Ki-67 expression in Non-invasive & Invasive urothelial neoplasm. This retrospective study is done in the Department of Pathology of L.N. Medical College and J.K. Hospital, Bhopal. Urothelial Neoplasm cases diagnosed from January 2019 to January 2022 were included, & relevant clinico-pathological data and their Ki-67 Labelling Index was evaluated & correlated. Total 60 cases were studied, 30 had invasive carcinoma whereas, 30 had non-invasive neoplasm. Ki-67 expression (>13%) was seen maximum in invasive cancers i.e 40% cases, whereas (<13%) was seen maximum in non-invasive neoplasms i.e 38.3%. A statistically significant expression of Mean Ki-67 Labelling Index was observed that increased from papilloma to PUNLMP, Non- Invasive urothelial neoplasm Low grade & High grade in non-invasive urothelial neoplasm (p<0.001), and from lamina propria invasive to muscle invasive urothelial cancers (p=0.013). A Higher tumor proliferation of greater than 13% was significantly related to greater tumor size (p=0.04). Ki-67 labelling index being a measure of tumor proliferation is related to tumor histological grade. Large urothelial tumor size was associated to high Ki-67 LI and was not strongly associated with age and gender. Therefore Ki-67 expression can be used as Diagnostic & Prognostic marker in urothelial tumors.
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Salehi, Fateme, Anne Agur, Bernd W. Scheithauer, Kalman Kovacs, Ricardo V. Lloyd, and Michael Cusimano. "KI-67 IN PITUITARY NEOPLASMS." Neurosurgery 65, no. 3 (2009): 429–37. http://dx.doi.org/10.1227/01.neu.0000349930.66434.82.
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Alhosaini, Khaled, Mushtaq A. Ansari, Ahmed Nadeem, et al. "Dysregulation of Ki-67 Expression in T Cells of Children with Autism Spectrum Disorder." Children 8, no. 2 (2021): 116. http://dx.doi.org/10.3390/children8020116.
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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by behavioral abnormalities such as impairments in social function and deficits in communication. The etiology of autism is unknown in most cases, but many studies have pointed towards the immune system as a causative agent in autism. Specific studies implicated lymphocytes, natural killer (NK) cells, monocytes, cytokines, and specific transcription factors in the development of ASD. The protein Ki-67 is n expressed in the proliferating cells and is used as a tool in several disorders. Ki-67 plays a crucial role in many neurological diseases. However, Ki-67 role in ASD is not fully understood. In this study, we investigated the possible role of Ki-67 expression in autistic children. We compared Ki-67 production in CD3+, CD4+, CD8+, CXCR4+, CXCR7+, CD45R+, HLA-DR+, GATA3+, Helios+, and FOXP3+ peripheral blood mononuclear cells (PBMCs) in autistic children to typically developing (TD) controls using immunofluorescence staining. We also determined Ki-67 mRNA levels in PBMCs using RT–PCR. The results revealed that autistic children had significantly increased numbers of CD3+Ki-67+, CD4+Ki-67+, CD8+Ki-67+, CXCR4+Ki-67+, CXCR7+Ki-67+, CD45R+Ki-67+, HLA-DR+Ki-67+, CXCR4+GATA3+, GATA3+Ki-67+ cells and decreased Helios+Ki-67+ and FOXP3+Ki-67+ cells compared with TD controls. In addition, the autistic children showed upregulation of Ki-67 mRNA levels compared with TD controls. Further studies need to be carried out to assess the exact role of Ki-67 and its therapeutic potential in ASD.
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Kolles, Harry, Winfried F�rderer, Rudolf Bock, and Wolfgang Feiden. "Combined Ki-67 and feulgen stain for morphometric determination of the Ki-67 labelling index." Histochemistry 100, no. 4 (1993): 293–96. http://dx.doi.org/10.1007/bf00270049.
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Manoir, Stanislas Du, Philippe Guillaud, Emmanuel Camus, Daniel Seigneurin, and Gérard Brugal. "Ki-67 labeling in postmitotic cells defines different Ki-67 pathways within the 2c compartment." Cytometry 12, no. 5 (1991): 455–63. http://dx.doi.org/10.1002/cyto.990120511.
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Lee, Janghee, Young-jin Lee, Soong June Bae, et al. "Ki-67, 21-Gene Recurrence Score, Endocrine Resistance, and Survival in Patients With Breast Cancer." JAMA Network Open 6, no. 8 (2023): e2330961. http://dx.doi.org/10.1001/jamanetworkopen.2023.30961.
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ImportanceBoth high 21-gene recurrence score (RS) and high Ki-67 level are poor prognostic factors in patients with estrogen receptor (ER)–positive ERBB2-negative (ER+/ERBB−) breast cancer; however, a discrepancy between the 2 has been noted. Survival differences according to these 2 biomarkers are not well known.ObjectiveTo assess the associations between RS and Ki-67 expression and between Ki-67 expression and recurrence-free survival in patients with ER+/ERBB− breast cancer with low RS.Design, Setting, and ParticipantsThis cohort study included women treated for ER+/ERBB2− breast cancer who underwent the 21-gene RS test from March 2010 to December 2020 in 2 hospitals in Korea.ExposuresRecurrence score and Ki-67 level.Main Outcomes and MeasuresA Cox proportional hazards regression model was used to examine the association of Ki-67 with recurrence-free survival (RFS), while a binary logistic regression model was used to examine the association between Ki-67 and secondary endocrine resistance. High Ki-67 expression was defined as 20% or greater, and low genomic risk as an RS of 25 or less. Secondary endocrine resistance was defined as breast cancer recurrence that occurred after at least 2 years of endocrine therapy and during or within the first year after completing 5 years of adjuvant endocrine therapy.ResultsA total of 2295 female patients were included (mean [SD] age, 49.8 [9.3] years), of whom 1948 (84.9%) were in the low genomic risk group and 1425 (62.1%) had low Ki-67 level. The median follow-up period was 40 months (range, 0-140 months). The RS and Ki-67 level had a moderate correlation (R = 0.455; P &amp;lt; .001). Of the patients with low Ki-67 level, 1341 (94.1%) had low RS, whereas 607 of 870 patients with high Ki-67 level (69.8%) had low RS. In patients with low RS, the RFS differed significantly according to Ki-67 level (low Ki-67, 98.5% vs high Ki-67, 96.5%; P = .002). Among the 1807 patients with low genomic risk who did not receive chemotherapy, high Ki-67 level was independently associated with recurrence (hazard ratio, 2.51; 95% CI, 1.27-4.96; P = .008). Recurrence after 3 years differed significantly according to Ki-67 level (low Ki-67, 98.7% vs high Ki-67, 95.7%; P = .003), whereas recurrence within 3 years did not differ (low Ki-67, 99.3% vs high Ki-67, 99.3%; P = .90). In addition, Ki-67 was associated with secondary endocrine resistance in patients with low RS who did not receive chemotherapy (odds ratio, 2.49; 95% CI, 1.13-5.50; P = .02).Conclusions and RelevanceIn this cohort study of patients with ER+/ERBB2− breast cancer, a moderate correlation was observed between Ki-67 and RS, and high Ki-67 level in patients with low genomic risk was associated with increased risk of secondary endocrine resistance.
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Munakata, S., and J. B. Hendricks. "A multilabeling technique for simultaneous demonstration and quantitation of Ki-67 and nucleolar organizer regions (AgNORs) in paraffin-embedded tissue." Journal of Histochemistry & Cytochemistry 42, no. 6 (1994): 789–93. http://dx.doi.org/10.1177/42.6.7514625.
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Although many investigators have demonstrated a relationship between argyrophilic nucleolar organizer regions (AgNORs) and Ki-67 expression in solid tumors, no previous studies have simultaneously assessed the relationship between AgNOR and Ki-67 expression in paraffin-embedded tissue. We describe a method for simultaneous demonstration and quantitation of Ki-67 and AgNORs in routinely processed tissue. The Ki-67 equivalent monoclonal antibody MIB1, which can detect proliferative activity in routinely processed tissue with microwave heating, was employed. Fresh human tonsil tissue was fixed in formalin and embedded in paraffin for Ki-67/AgNOR dual staining. Image analysis was employed for quantitation of AgNOR staining in Ki-67-positive and Ki-67-negative nuclei. The double-staining procedure had no measurable effect on the individual parameters: Ki-67 labeling index, mean AgNOR number (NN), and NOR percentage nuclear area (NPNA). However, microwave processing for Ki-67 immunostaining significantly increased nuclear area (NA) and AgNOR area (AA). A significant difference was found between Ki-67-positive and Ki-67-negative cells for NN (p < 0.001), NA (p < 0.001), AA (p < 0.001), and NPNA (p < 0.001). These results suggest a direct relationship between AgNOR and Ki-67 in paraffin-embedded tissue.
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Kamrava, Mitchell, Shane Mesko, Robyn Banerjee, Jiaoti Huang, D. Jeffrey Demanes, and Leonard S. Marks. "Quantifying the ki-67 heterogeneity profile in prostate cancer." Journal of Clinical Oncology 31, no. 6_suppl (2013): 73. http://dx.doi.org/10.1200/jco.2013.31.6_suppl.73.
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73 Background: Ki-67 is a robust predictive/prognostic marker in prostate cancer however tumor heterogeneity may compromise its clinical utility when Ki-67 is determined off of prostate biopsy samples. We examined the variation of Ki-67 in prostate biopsy samples by NCCN risk groups and the location of the highest Ki-67 relative to the most dominant lesion on multiparametric (MP) MRI. Methods: An IRB approved retrospective analysis was done on 77 consecutive men whose prostate biopsies revealed cancer. Using a MRI/US fusion device (Artemis), biopsy cores were obtained systematically and when MRI indicated a lesion, by targeting. Ki-67 staining was determined by a manual semi-quantitative method and reported as % of positive cells. The highest Ki-67 per patient was used to determine inter-prostatic variation. Ki-67 range (highest Ki-67 minus lowest Ki-67 value) was used to determine intra-prostatic variation on a subset of 47 patients with ≥2 positive biopsy cores. Ki-67 range was also used to evaluate intra-lesion variation on 31 MP MRI defined lesions with > 1 targeted positive biopsy core. The relationship of the dominant lesion (lesion with the largest tumor diameter) to the highest Ki-67 in the entire prostate was examined for 10 patients with ≥2 distinct lesions on MP MRI. Analysis of variance (ANOVA) was used to evaluate differences between the means of NCCN-defined risk groups. Results: Inter-prostatic Ki-67 mean±standard deviation (SD) values for low, intermediate and high risk patients were 5.1% ± 3.8%, 7.4% ± 6.8%, and 12.0% ± 12.4% (ANOVA p=0.01). Intra-prostatic mean±SD Ki-67 ranges in low, intermediate, and high risk patients were 2.6% ± 3.4%, 4.6% ± 6.4%, 9.5% ± 10.6% (ANOVA p = 0.0246). Intra-lesion mean±SD Ki-67 ranges in low, intermediate and high risk patients were 1.0%±1.0%, 4.0%±4.29%, and 6.7%±11.51% (ANOVA p=0.39). The dominant lesion harbored the highest Ki-67 30% of the time. Conclusions: High risk patients have significantly higher inter- and intra-prostatic Ki-67 heterogeneity profiles than men with low/intermediate risk disease. The highest Ki-67 is often not located in the dominant MRI defined lesion. This data can inform future biopsy strategies when integrating Ki-67 into clinical practice.
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Vukelic, J., R. Dobrila-Dintinjana, A. Dekanic, B. Marijic, A. Cubranic, and T. Braut. "The Relevance of Assessing the Cell Proliferation Factor Ki-67 in Squamous Cell Carcinoma of the Larynx." BioMed Research International 2019 (January 15, 2019): 1–6. http://dx.doi.org/10.1155/2019/8142572.
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The aim of study was to investigate the expression of the proliferation factor Ki-67 and its relationship with histological grade, cancer stage, and treatment outcome in squamous cell carcinoma of the larynx. Samples from 78 patients with laryngeal cancer were analysed retrospectively. Paraffin sections of tumors were immunohistochemically stained for Ki-67 expression. The patients were divided in two groups according to the proliferative factor values (a low Ki-67 index group - Ki-67≤34 and high Ki-67 index group-Ki-67 >34). Statistical analysis of the data shows significant correlation among histological tumor grade and the value of the Ki-67 proliferative index. There was no correlation between tumoral Ki-67 expression and diagnosis, stage of the disease, or treatment outcome. In conclusion, Ki-67 expression in laryngeal cancer is not the most reliable marker for making precise diagnosis and predicting the clinical course.
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Đokić, Snežana, Barbara Gazić, Biljana Grčar Kuzmanov, et al. "Clinical and Analytical Validation of Two Methods for Ki-67 Scoring in Formalin Fixed and Paraffin Embedded Tissue Sections of Early Breast Cancer." Cancers 16, no. 7 (2024): 1405. http://dx.doi.org/10.3390/cancers16071405.
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Proliferation determined by Ki-67 immunohistochemistry has been proposed as a useful prognostic and predictive marker in breast cancer. However, the clinical validity of Ki-67 is questionable. In this study, Ki-67 was retrospectively evaluated by three pathologists using two methods: a visual assessment of the entire slide and a quantitative assessment of the tumour margin in 411 early-stage breast cancer patients with a median follow-up of 26.8 years. We found excellent agreement between the three pathologists for both methods. The risk of recurrence for Ki-67 was time-dependent, as the high proliferation group (Ki-67 ≥ 30%) had a higher risk of recurrence initially, but after 4.5 years the risk was higher in the low proliferation group. In estrogen receptor (ER)-positive patients, the intermediate Ki-67 group initially followed the high Ki-67 group, but eventually followed the low Ki-67 group. ER-positive pN0-1 patients with intermediate Ki-67 treated with endocrine therapy alone had a similar outcome to patients treated with chemotherapy. A cut-off value of 20% appeared to be most appropriate for distinguishing between the high and low Ki-67 groups. To summarize, a simple visual whole slide Ki-67 assessment turned out to be a reliable method for clinical decision-making in early breast cancer patients. We confirmed Ki-67 as an important prognostic and predictive biomarker.
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Choi, Soon Bo, Jung Min Park, Jee Hyun Ahn, et al. "Ki-67 and breast cancer prognosis: does it matter if Ki-67 level is examined using preoperative biopsy or postoperative specimen?" Breast Cancer Research and Treatment 192, no. 2 (2022): 343–52. http://dx.doi.org/10.1007/s10549-022-06519-1.
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Abstract Purpose This study aimed to identify the association between Ki-67 level and the prognosis of patients with breast cancer, regardless of the timing of Ki-67 testing (using preoperative biopsy vs. postoperative specimen). Methods A total of 4177 patients underwent surgery between January 2008 and December 2016. Immunohistochemical Ki-67 levels, using either preoperative (1673) or postoperative (2831) specimens, were divided into four groups using cutoff points of 10%, 15%, and 20%. Results Groups with higher-Ki-67 levels, in both the pre- and postoperative periods, showed significantly larger tumor size, higher grade, more frequent hormone receptor-negativity and human epidermal growth factor receptor 2 overexpression, and active adjuvant treatments than groups with lower-Ki-67 levels. High-Ki-67 levels were also significantly associated with poor survival, irrespective of the timing of specimen examination. Conclusion Despite the problems associated with Ki-67, Ki-67 level is an important independent prognostic factor, regardless of the timing of Ki-67 testing, i.e., preoperative or postoperative testing.
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Dmitrenko, A. P. "Lateral differences of breast cancer proliferative activity (KI-67)." Kazan medical journal 97, no. 4 (2016): 550–55. http://dx.doi.org/10.17750/kmj2015-550.
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Aim. To determine lateral differences of breast cancer proliferative activity Ki-67.Methods. According to immunohistochemical study protocols analysis of material of 500 patients with breast cancer was conducted. In primary tumors estrogen and progesterone receptors expression, Ki-67, C-erbB-2 was studied.Results.Using two-way analysis of variance, it was found that Ki-67 index was significantly influenced by both side of the tumor lesion (p=0.009) and age of patients (p=0.0002). A higher Ki-67 corresponded to right-sided cancer localization. Statistically significant age differences of Ki-67 index are marked only in right-sided cancer (pConclusion. Statistically significant difference of Ki-67 index in right- and left-sided breast cancer was found, significantly higher Ki-67 was detected in the right-sided tumors, Ki-67 are present only in patients before 60 years.
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Mizuno, Yoshio, Hiroyuki Takayanagi, Hiroaki Abe, and Kazuhiko Sato. "Standardization of Ki-67 assessment for breast cancer patients with preoperative endocrine therapy." Journal of Clinical Oncology 30, no. 15_suppl (2012): e11007-e11007. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e11007.
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e11007 Background: Change in Ki-67 levels is a predictive marker of breast cancer, and it has been widely investigated in patients treated with preoperative endocrine therapy. Several studies have compared Ki-67 expression in untreated specimens obtained by core needle biopsy (CNB) and surgery. We conducted a retrospective study to assess Ki-67 expression between these two specimen types. Methods: 307 patients underwent primary operations for early breast cancer at Tokyo-West Tokushukai Hospital from August 2008 to October 2011. Among them, 193 patients who underwent CNB prior to the operation were enrolled. Patients with ductal carcinoma in situ and those undergoing neoadjuvant chemotherapy were excluded. A cutoff value of 20% was used as the Ki-67 positive criterion. We also examined ER, PgR, and HER2 expression and compared it with Ki-67 expression. Statistical significance for concordance rates between the two types of specimens was evaluated by Wilcoxon t-test. To evaluate the consequences of formalin and genetic heterogeneity, parameters such as operative method and tumor size were analyzed using chi-square test. We reexamined Ki-67 expression in the central laboratory among the Ki-67 discordant group to evaluate the discordance between the pathologist’s judgments. Results: The Ki-67 expression concordance rate between the two types of specimens was 77.7%, which was significantly lower than that for ER, PgR, and HER2 expression at 94.8%, 88%, and 91%, respectively. No significant differences in the operative method (mastectomy vs. breast conserving surgery) or tumor size (≤2cm vs. >2cm) were observed between the groups. We reexamined Ki-67 expression in the Ki-67 discordant group and found that the Ki-67 concordance rate had improved to 93.8%. Conclusions: The Ki-67 expression concordance rate between the two types of specimens was significantly lower than that of ER, PgR, and HER2 expression. However, a reexamination of Ki-67 expression in the central laboratory revealed no significant difference, suggesting the need for a standard pathological assessment of Ki-67 expression to clinically use Ki-67 as a predictive marker.
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Fulton, Regan. "Getting a Grip on Ki-67." Applied Immunohistochemistry & Molecular Morphology 29, no. 2 (2021): 83–85. http://dx.doi.org/10.1097/pai.0000000000000908.
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Chirieac, Lucian R. "Ki-67 expression in pulmonary tumors." Translational Lung Cancer Research 5, no. 5 (2016): 547–51. http://dx.doi.org/10.21037/tlcr.2016.10.13.
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Hendricks, James B., Edward J. Wilkinson, Paul Kubilis, Peter Drew, Susan M. Blaydes, and Satoru Munakata. "Ki-67 Expression in Vulvar Carcinoma." International Journal of Gynecological Pathology 13, no. 3 (1994): 205–10. http://dx.doi.org/10.1097/00004347-199407000-00003.
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Meyer, John S. "Thymidine Labeling Index Versus Ki-67." American Journal of Clinical Pathology 95, no. 4 (1991): 602–3. http://dx.doi.org/10.1093/ajcp/95.4.602b.
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Ramondetta, L., C. J. Dunton, K. H. van Hoeven, A. J. Kovatich, and M. Bibbo. "Ki-67 Immunoreactivity in Endocervical Lesions." Journal of Lower Genital Tract Disease 1, no. 1 (1997): 28. http://dx.doi.org/10.1097/00128360-199701000-00030.
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Mooy, Cornelia M., Paul T. V. M. De Jong, Theodorus H. Van Der Kwast, Paul G. H. Mulder, Martine J. Jager, and Dirk J. Ruiter. "Ki-67 Immunostaining in Uveal Melanoma." Ophthalmology 97, no. 10 (1990): 1275–80. http://dx.doi.org/10.1016/s0161-6420(90)32420-x.
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Shalini, P., Natrajan Suresh, and Hemalatha Ganapathy. "Ki-67 Expression in Endometrial Hyperplasia." Indian Journal of Public Health Research & Development 10, no. 11 (2019): 4050. http://dx.doi.org/10.5958/0976-5506.2019.04232.3.
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Lindboe, C. F., and S. H. Torp. "Comparison of Ki-67 equivalent antibodies." Journal of Clinical Pathology 55, no. 6 (2002): 467–71. http://dx.doi.org/10.1136/jcp.55.6.467.
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&NA;. "Ki-67 and recurrences of chordomas." Advances in Anatomic Pathology 4, no. 5 (1997): 325. http://dx.doi.org/10.1097/00125480-199709000-00036.
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Trihia, Helen, Susan Murray, Karen Price, et al. "Ki-67 expression in breast carcinoma." Cancer 97, no. 5 (2003): 1321–31. http://dx.doi.org/10.1002/cncr.11188.
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Yang, Hyeon Seok, Yunseob Hwang, Yongeun Lee, et al. "Abstract 2308: Semi-automated Ki-67 index assessment using top-k hotspot recommendation in Ki-67 IHC stained WSIs." Cancer Research 84, no. 6_Supplement (2024): 2308. http://dx.doi.org/10.1158/1538-7445.am2024-2308.
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Abstract Ki-67 index is commonly used as a breast cancer proliferation marker. However, it is a laborious and time-consuming task for a pathologist to directly measure the Ki-67 index. Recently, automation techniques using machine learning techniques such as deep learning have been proposed. In this study, we propose a top-k hotspot recommendation method to help Ki-67 index assessment based on nuclei detection detected by a deep learning model. The dataset included a total of 32 diaminobenzidine-hematoxylin (DAB-H) Ki-67 IHC whole slide images (WSIs) of breast cancer obtained by core biopsy. Each of these WSIs was evaluated by a pathologist using the interval of the Ki-67 index estimate and the scores of 1+, 2+, 3+, and 4+. Additionally, the search area was manually designated to exclude internal control. We developed a Ki-67 index analysis model based on deep learning and image analysis. Nuclei segmentation used the StarDist model. The detected results were filtered based on nucleus size and nucleus eccentricity. The filtering threshold was determined experimentally. To recommend top-k hotspots, a coarse search is performed to move the circle region horizontally and vertically in specific units, and the top k regions based on Ki-67 index are found among areas containing more than 500 cells. Next, a fine search is performed around the k areas in detail. Finally, the top-k hotspots and each detected positive and negative cells, count of positive cells and negative cells, and predicted Ki-67 index are provided. It was confirmed that the Ki-67 score estimated for the detected top-1 hotspot and the pathologist's Ki-67 score had a correlation of Pearson correlation coefficient=0.8153, R2=0.6648. As k increased, the top-k accuracy was observed to increase from 68.75% when k = 1 and 3 to 75.00% when k = 5, based on the pathologist's score. When a pathologist reviewed 10 cases where the Ki-67 score differed from the prediction, 6 cases were judged to be worth reexamining considering the proposed hotspot and Ki-67 index, and 2 cases included stromal cells in cell detection. In two cases, the WSI was judged to be blurry. Cell analysis and top-k hotspot recommendation using deep learning and image analysis were performed on Ki-67 IHC stained WSIs and compared with the pathologist's Ki-67 score. Through semi-automatic top-k hotspot recommendation, the reliability of diagnosis can be increased as an auxiliary test to Ki-67 index assessment. Citation Format: Hyeon Seok Yang, Yunseob Hwang, Yongeun Lee, Kyungsoo Jung, Minjung Sung, Tae-Yeong Kwak, Sun Woo Kim, Hyeyoon Chang. Semi-automated Ki-67 index assessment using top-k hotspot recommendation in Ki-67 IHC stained WSIs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2308.
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Soebjanto, Sonny. "Correlation of EGFR, RAS, ERK and Ki-67 as predictor of inverted papilloma malignancy transformation." Oto Rhino Laryngologica Indonesiana 50, no. 2 (2021): 107. http://dx.doi.org/10.32637/orli.v50i2.343.
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ABSTRACTBackground: Inverted papilloma (IP) is benign tumor of the nasal cavity and paranasal sinuses epithelium. Sinonasal squamous cell carcinoma (SCC) is epithelial malignancy of nasal cavity and paranasal sinuses. HPV increases epidermal growth factor receptor (EGFR) expression mediated by E5. RAS is part of the RAS-RAF-MEK-ERK pathway that regulates various cell functions. Ki-67 serves as a molecular marker of tumor proliferation. Early malignant transformation often goes unnoticed. It is important to know the roles of EGFR, RAS, ERK and Ki-67 as predictor for tumor markers in IP and Sinonasal SCC. Objective: To find out the correlation of EGFR, RAS, ERK expressions towards Ki-67 expression as predictor of sinonasal IP transformation into sinonasal SCC. Method: A cross sectional study taking samples from the medical record of Dr.Saiful Anwar Hospital. The expression of EGFR, RAS, ERK and Ki-67 were examined with immunohistochemistry. Result: The estimated inner model results for direct influence of EGFR, RAS, ERK and Ki-67 towards IP and SCC were 2.352, 2.019, 2.625, and 2.213. The estimated inner model results for direct influence of EGFR, RAS and ERK towards Ki- 67 were 2.386, 3.811, and 3.00. Discussion: Previous research had reported an increase in Ki-67 index indicated the role of Ki-67 in cell tranformation of IP with dysplasia into SCC. Conclusion: EGFR, RAS and ERK expressions related to Ki-67 on IP and SCC. Increased expressions of EGFR, RAS, ERK and Ki-67 on IP indicated risk of malignant transformation. EGFR, RAS, ERK and Ki-67 could become predictors of IP transformation into SCC. ABSTRAKLatar belakang: Papiloma inverted (PI) merupakan tumor jinak epitel kavum nasi dan sinus paranasal. Karsinoma sel skuamosa (KSS) sinonasal merupakan keganasan yang berasal dari epitel mukosa kavum nasi dan sinus paranasal. HPV meningkatkan ekspresi EGFR yang dimediasi oleh E5. RAS merupakan bagian dari jaras RAS–RAF–MEK–ERK yang mengatur berbagai fungsi sel. Ki-67 berfungsi sebagai penanda molekuler proliferasi tumor. Diagnosis dini transformasi keganasan pada papiloma inverted seringkali luput dari pengamatan. Penting mengetahui peran EGFR, RAS, ERK dan Ki-67 sebagai cikal bakal penanda tumor pada IP dan KSS sinonasal. Tujuan: Mengetahui hubungan ekspresi EGFR, RAS, ERK terhadap Ki-67 sebagai prediksi transformasi keganasan PI sinonasal menjadi KSS sinonasal. Metode: Penelitian cross sectional, sampel penelitian diambil dari arsip rekam medis rawat jalan yang masih didapatkan preparat histopatologi papiloma inverted dan karsinoma sel skuamosa sinonasal di laboratorium Patologi Anatomi, dan dilakukan pemeriksaan ekspresi EGFR, RAS, ERK dan Ki-67 dengan imunohistokimia. Hasil: Hasil estimasi inner model untuk pengaruh langsung EGFR, RAS, ERK dan Ki-67 terhadap PI dan KSS sebesar 2,352, 2,019, 2,625 dan 2,213. Hasil estimasi inner model untuk pengaruh langsung EGFR, RAS dan ERK terhadap Ki-67 sebesar 2,386, 3,811 dan 3,00. Diskusi: Penelitian terdahulu membuktikan peningkatan indeks Ki-67 merupakan pertanda adanya peran Ki-67 pada perubahan PI dengan displasia menjadi SCC. Kesimpulan: Ekspresi EGFR, RAS dan ERK berhubungan terhadap Ki-67 pada IP dan KSS. Peningkatan ekspresi EGFR, RAS, ERK dan Ki-67 pada PI menandakan adanya risiko terjadi transformasi keganasan. EGFR, RAS, ERK dan Ki-67 dapat menjadi cikal bakal prediktor transformasi keganasan PI menjadi KSS.
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Pranjali, Chatpalli, Kamath Sulatha, and Mysorekar Vijaya V. "CDX2 and Ki-67 Expression in Gastric Carcinoma and Its Association with Clinocopathological Parameters." Asian Pacific Journal of Cancer Biology 7, no. 3 (2022): 255–63. http://dx.doi.org/10.31557/apjcb.2022.7.3.255-263.
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Background: CDX2 has been established as a good prognostic marker for colorectal carcinomas. Differentiated adenocarcinomas are characterized by higher CDX2 expression than undifferentiated tumors with stronger reactivity in intestinal phenotypes. There is a close correlation between the degree of tumor differentiation and the Ki-67 score. It was also observed that strong CDX2 expression was associated with low Ki-67 index whereas negative or dim CDX2 expression was associated with high Ki-67 index. Methods: Gastric biopsies and gastrectomy specimens with gastric carcinoma were evaluated clinicopathologically and processed for immunohistochemistry (IHC) staining to assess CDX2 and Ki-67 expression. The relationship between 2 markers and each clinicopathological parameter was evaluated. Data was statistically analysed. P<0.05 were taken for statistical significance. Results: The study was done on 57 gastric adenocarcinoma cases with mean age 56.12 years. No significant correlation was found between CDX2 & Ki-67 with clinical, gross & microscopic parameters except for tumor location and depth of invasion. Significant correlation was detected between CDX2 (p=0.04) & Ki-67 (p=0.03) with tumor location. Depth of tumor invasion was significantly associated with Ki-67 (p=0.013). No significant association between CDX2 and Ki-67 was observed. Conclusion: The statistical correlation between CDX2 & Ki-67 with clinicopathological parameters proves that CDX2 & Ki-67 to be the independent markers with respect to tumor site and depth of invasion (in case of Ki-67). But due to lack of association of CDX2 with Ki-67 further studies need to be done with higher sample size.
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Zheng, Jianqing, Bifen Huang, Ying Chen, Bingwei Zeng, Lihua Xiao, and Min Wu. "Exploratory analyses of the associations between Ki-67 expression, lymph node metastasis, and prognosis in patients with esophageal squamous cell cancer." PeerJ 13 (February 26, 2025): e19062. https://doi.org/10.7717/peerj.19062.
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Background The relationships between Ki-67/MKI67 expression, lymph node metastasis (LNM), vascular invasion (VI), and perineural invasion (PI) in esophageal squamous cell cancer (ESCC) remain unclear. This retrospective cohort study was performed to evaluate the prognostic value of Ki-67 expression and its association with LNM in patients with resected ESCC. Methods The analysis included 168 patients with ESCC with available Ki-67 protein expression data. The patients were divided into Ki-67 high-expression group (Ki-67 High, 93 cases) and Ki-67 low-expression (Ki-67 Low, 75 cases) groups. Associations between Ki-67 expression and ESCC pathological features was assessed using chi-square test. Overall survival (OS) was compared between the two groups using Kaplan–Meier survival analysis and Cox proportional hazards model. Results Median follow-up duration was 33.5 months (range 3.0–60.0 months). High Ki-67 expression was significantly associated with poor OS in patients with ESCC compared to that of the low-expression in both univariate (hazard ratios (HR) = 3.42, 95% CI [2.22–5.27], P < 0.001) and multivariate analyses (HR = 1.98, 95% CI [1.33–2.94], P < 0.001). Furthermore, high Ki-67 expression was significantly associated with an increased risk of LNM (χ2 = 11.219, P = 0.011), VI (χ2 = 6.359, P = 0.012), and PI (χ2 = 8.877, P = 0.003). Conclusions High Ki-67 protein expression is associated with poor prognosis in ESCC. Increased Ki-67 expression significantly increases the risk of LNM, VI, and PI in ESCC, and thus may serve as an indication for adjuvant therapy in ESCC management.
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Milev, Hristo S., Vasil Nanev, Desislava Dimitrova, et al. "Evaluation of Ki-67 index in breast cancer cases with intratumor heterogeneity." Journal of Biomedical and Clinical Research 17 (June 10, 2024): 53–58. https://doi.org/10.3897/jbcr.e126709.
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There are no specific recommendations for evaluating the Ki-67 index in heterogeneous breast carcinomas. This study aimed to evaluate the applicability of currently accepted recommendations for Ki-67 evaluation in breast cancer in the context of intratumor heterogeneity. Twelve cases of heterogeneous breast carcinomas obtained from 110 patients were retrospectively studied. Ki-67 staining was performed according to protocols provided by the reagent manufacturer. Results for Ki-67 of the separate components in each tumor were obtained, described, and analyzed statistically using a paired t-test. Values of <em>p</em> < 0.05 were considered as statistically significant. SPSS software was used for statistical analysis. Results from the comparison of the Ki-67 index evaluation in each heterogeneous component of the studied tumors demonstrated no statistically significant difference of mean values <em>t</em> = 0.4802, <em>p</em> = 0.6405. The anticipation of an average Ki-67 score in the evaluated cases would have changed the molecular subtype from Luminal B to Luminal A (due to the Ki-67 index below 14%) in two of the cases. Heterogeneous tumors had a different Ki-67 index in their separate components. Our observations suggest that Ki-67 in heterogeneous breast carcinoma is evaluated and reported separately for the distinguishable tumor components.
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Ingolf, Juhasz-Böss, Mavrova Russalina, Moga Simona, et al. "Can Ki-67 Play a Role in Prediction of Breast Cancer Patients' Response to Neoadjuvant Chemotherapy?" BioMed Research International 2014 (2014): 1–7. http://dx.doi.org/10.1155/2014/628217.
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Background. Currently the choice of breast cancer therapy is based on prognostic factors. The proliferation marker Ki-67 is used increasingly to determine the method of therapy. The current study analyses the predictive value of Ki-67 in foreseeing breast cancer patients’ responses to neoadjuvant chemotherapy.Methods. This study includes patients with invasive breast cancer treated between 2008 and 2013. The clinical response was assessed by correlating Ki-67 to histological examination, mammography, and ultrasonography findings.Results. The average Ki-67 value in our patients collectively (n=77) is 34.9 ± 24.6%. The average Ki-67 value is the highest with 37.4 ± 24.0% in patients with a pCR. The Ki-67 values do not differ significantly among the 3 groups: pCR versus partial pathological response versus stable disease/progress (P=0.896). However, Ki-67 values of patients with luminal, Her2 enriched, and basal-like cancers differed significantly from each other. Furthermore, within the group of luminal tumors Ki-67 values of patients with versus without pCR also differed significantly.Conclusion. Our data shows that the Ki-67 value predicts the response to neoadjuvant chemotherapy as a function of the molecular subtype, reflecting the daily routine concerning Ki-67 and its impressing potential and limitation as a predictive marker for neoadjuvant chemotherapy response.
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Crispino, Sergio, Ambrogio Brenna, Daniela Colombo, et al. "Ki-67 Labeling Index in Breast Cancer." Tumori Journal 75, no. 6 (1989): 557–62. http://dx.doi.org/10.1177/030089168907500608.
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Measurements of cell cycle kinetics have been found to correlate with the clinical course of patients with breast cancer. However, the thymidine labeling index and more rapid methods like flow cytometry remain complicated and costly. We assessed cell proliferation of 67 breast carcinomas by an immunoperoxidase procedure using a monoclonal antibody, Ki-67, which reacts with a nuclear antigen in proliferating cells. The percentage of Ki-67 positive cells ranged from 2% to 70 %. Tumors with high mitotic rate, high nuclear grade, high histologic grade, and negative estrogen receptors had statistically higher Ki-67 labeling rates. We found no significant differences between the Ki-67 labeling rate and other clinical (age at diagnosis, menopausal status) or pathologic (necrosis, fibrosis, vascular invasion, lymphatic invasion, cellular reaction, tumor size, lymph node metastases) features assessed. These results parallel previously reported data, and confirm that this immunohistochemical staining of breast carcinoma by Ki-67 monoclonal antibody can be considered a rapid and convenient method for assessing cell cycle kinetics. However, further studies, evaluating the correlation between Ki-67 labeling rate and prognosis are needed to better define the real usefulness of this analysis in clinical practice.
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LAURILA, RIIKKA E., TOM O. BÖHLING, CARL P. BLOMQVIST, et al. "Visual Counting and Automated Image-analytic Assessment of Ki-67 and their Prognostic Value in Synovial Sarcoma." Cancer Diagnosis & Prognosis 2, no. 1 (2022): 7–14. http://dx.doi.org/10.21873/cdp.10070.
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Background: Ki-67 is a widely used proliferation marker reflecting prognosis in various tumors. However, visual assessment and scoring of Ki-67 suffers from marked inter-observer and intra-observer variability. We aimed to assess the concordance of manual counting and automated image-analytic scoring methods for Ki-67 in synovial sarcoma. Patients and Methods: Tissue microarrays from 34 patients with synovial sarcoma were immunostained for Ki-67 and scored both visually and with 3DHistech QuantCenter. Results: The automated assessment of Ki-67 expression was in good agreement with the visually counted Ki-67 (rPearson=0.96, p<0.001). In a Cox regression model automated [hazard ratio (HR)=1.047, p=0.024], but not visual (HR=1.063, p=0.053) assessment method associated high Ki-67 scores with worse overall survival. Conclusion: The automated Ki-67 assessment method appears to be comparable to the visual method in synovial sarcoma and had a significant association to overall survival.
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Von Minckwitz, Gunter, Berit Mueller, Jens U. Blohmer, et al. "Prognostic and predictive impact of Ki-67 before and after neoadjuvant chemotherapy on PCR and survival: Results of the GeparTrio trial." Journal of Clinical Oncology 30, no. 15_suppl (2012): 1023. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.1023.
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1023 Background: We previously reported as a result of the GeparTrio phase III trial that response-guided neoadjuvant chemotherapy (CT) with TACx8 or TAC/NX, compared to TACx6, can improve survival especially in hormone-receptor (HR)-positive tumors. As this benefit could not be predicted by pathological complete response (pCR), better surrogate response markers are warranted. Methods: 2072 patients with operable or locally advanced breast cancer were treated with 2 cycles TAC before interim response assessment. Responders were randomized to additional TACx4 or TACx6 and non-responders to TACx4 or NXx4. We centrally measured Ki-67 in1165 pre-CT core biopsies and in 676 post-CT surgical samples. Counting patients with a pCR as having 0% Ki-67, 757 pre-/ post-CT pairs were available. Ki-67 percentage levels were grouped to low (0-15%), moderate (15.01-35%), and high (35.01-100%) according to cut-point finding analysis in a training and validation cohort. Results: pCR rates were 4.2%, 12.9%, and 29.0% in tumors with low, moderate, and high pre-CT Ki-67 levels (p<0.0001). Pre-CT Ki-67 levels significantly predicted disease-free survival (DFS) (log rank p<0.0001) overall, in the HR+ (p<0.0001), but not in the HR- (p=0.5) subgroup. Post-CT Ki-67 levels correlated with DFS (p<0.0001). Patients with low post-CT Ki-67 levels showed comparable outcome to patients with pCR. Patients with increased Ki-67 levels from before to after CT showed an impaired outcome compared to patients with stable or decreased Ki-67 levels (p<0.0001). However, post-CT Ki-67 levels appeared to have more prognostic relevance than Ki-67 changes. Low post-CT Ki-67 levels were not more frequent after response-guided treatments (response-guided vs conventional: p=0.153; TACx6 vs TACx8: p=0.335; TACx6 vs TAC/NX: p=0.420). Similar negative results were found for HR+ and HR- subgroups. Conclusions: Pre-CT Ki-67 levels are predictive for pCR and prognostic for DFS. Post-CT Ki-67 levels and changes between pre-and post-CT-Ki-67 levels are prognostic for DFS. As neither could predict different treatment effects on DFS, Ki67 cannot replace pCR as a surrogate marker for outcome after neo-adjuvant CT.
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Arifah, Arifah, Rafiq Sulistyo Nugroho, and Alfred J Petrarizky. "Ki-67 AS A PREDICTING FACTOR OF NASOPHARYNGEAL, BREAST, AND CERVICAL CANCER: A LITERATURE REVIEW." International Journal of Radiology and Imaging 3, no. 01 (2024): 26–34. http://dx.doi.org/10.21776//ub.ijri.2024.003.01.5.
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Background: Although the exact role remains unknown, Ki-67 is vital in cell division. Ki-67 is a nuclear nonhistone protein present in all active phases of the cell cycle. It has the potential to predict the prognosis of responsiveness to radiotherapy, chemotherapy, or endocrine therapy, estimate residual risk, and predict recurrence in many types of cancer, including nasopharyngeal cancer (NPC), breast cancer (BC), and cervical cancer (CX), and be a marker for treatment efficacy. We want to review the efficacy of Ki-67 as a predicting factor for three types of cancer, including NPC, breast, and cervical cancer, from several pieces of literature. Materials and Methods: We are conducting a literature review to describe the role of Ki-67 as a predicting factor in NPC, BC, and CX. Results: Pretreatment Ki-67 is used as an independent prognostic marker in NPC, and elevated values are associated with poor prognosis. High Ki-67 expression may indicate poorer recurrence-free survival and overall survival. A high Ki-67 index significantly correlated with adverse prognostic factors. Conclusion: A high expression of Ki-67 in NPC, breast cancer, and cervical cancer is associated with poor prognosis, poorer recurrence, and overall survival rates. Ki-67 can be considered as a valuable biomarker of many cancers. Keywords: Radiotherapy, Ki-67, nasopharyngeal cancer, breast cancer, cervical cancer
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Prueter, J., D. Norvell, and D. Backous. "Ki-67 index as a predictor of vestibular schwannoma regrowth or recurrence." Journal of Laryngology & Otology 133, no. 03 (2019): 205–7. http://dx.doi.org/10.1017/s0022215119000549.
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AbstractBackgroundKi-67 is a monoclonal antibody that provides a means of evaluating the growth fraction of normal and neoplastic human cell populations. A Ki-67 index of less than 3 per cent is expected for a typical schwannoma. Vestibular schwannomas with an index of greater than 3 per cent are presumed to be actively proliferating and pose a theoretically higher risk for regrowth or recurrence.MethodsA retrospective chart review was conducted. Ki-67 staining was performed and specimens were divided into two groups according to Ki-67 activity: less than 3 per cent (low index), and 3 per cent or greater (elevated index).ResultsEight patients (53.3 per cent) with elevated Ki-67 had recurrence or regrowth, versus five (8.5 per cent) in the low Ki-67 group. Among the 13 patients with recurrence or regrowth, the average Ki-67 value was 4.3 per cent. Among the 61 patients without recurrence or regrowth, the average Ki-67 value was 1.0 per cent.ConclusionThe Ki-67 labelling index reliably identifies vestibular schwannomas with an elevated potential for recurrence or regrowth in subtotal or total resection cases. In patients with a Ki-67 index greater than 3 per cent, more frequent clinical examination and radiological follow up are recommended.
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Mesko, Shane, Patrick Kupelian, D. Jeffrey Demanes, Jaoti Huang, Pin-Chieh Wang, and Mitchell Kamrava. "Quantifying the Ki-67 Heterogeneity Profile in Prostate Cancer." Prostate Cancer 2013 (2013): 1–5. http://dx.doi.org/10.1155/2013/717080.
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Background:Ki-67 is a robust predictive/prognostic marker in prostate cancer; however, tumor heterogeneity in prostate biopsy samples is not well studied.Methods:Using an MRI/US fusion device, biopsy cores were obtained systematically and by targeting when indicated by MRI. Prostate cores containing cancer from 77 consecutive men were analyzed. The highest Ki-67 was used to determine interprostatic variation. Ki-67 range (highest minus lowest) was used to determine intraprostatic and intralesion variation. Apparent diffusion coefficient (ADC) values were evaluated in relation to Ki-67.Results:Interprostatic Ki-67 mean ± standard deviation (SD) values for NCCN low (L), intermediate (I), and high (H) risk patients were 5.1 ± 3.8%, 7.4 ± 6.8%, and 12.0 ± 12.4% (ANOVAP=0.013). Intraprostatic mean ± SD Ki-67 ranges in L, I, and H risk patients were 2.6 ± 3.6%, 5.3 ± 6.8%, and 10.9 ± 12.3% (ANOVAP=0.027). Intralesion mean ± SD Ki-67 ranges in L, I, and H risk patients were 1.1 ± 0.9%, 5.2 ± 7.9%, and 8.1 ± 10.8% (ANOVAP=0.22). ADC values at Ki-67 > and <7.1% were 860 ± 203 and 1036 ± 217, respectively (P=0.0029).Conclusions:High risk patients have significantly higher inter- and intraprostatic Ki-67 heterogeneity. This needs to be considered when utilizing Ki-67 clinically.
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Marcondes, Natália, Flavo Fernandes, and Gustavo Faulhaber. "Ki-67 expression in mature B-cell neoplasms: a flow cytometry study." Revista da Associação Médica Brasileira 64, no. 6 (2018): 525–29. http://dx.doi.org/10.1590/1806-9282.64.06.525.
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SUMMARY OBJECTIVE: Ki-67 is a nuclear protein associated with cellular proliferation in normal or leukemic conditions that can help identify more aggressive diseases and is usually evaluated with immunohistochemistry. The aim of this was to assess Ki-67 expression on mature B-cell neoplasms samples with flow cytometry immunophenotyping. METHOD: After surface staining with CD19 and CD45, intracellular staining for Ki-67 was performed in leukemic mature B-cells. Ki-67 expression was evaluated with flow cytometry. RESULTS: Ki-67 expression was higher in mantle cell lymphoma, Burkitt lymphoma, and diffuse large B-cell lymphoma cases. It was also associated with CD38 mean fluorescence intensity. CONCLUSIONS: Ki-67 expression evaluated by flow cytometry can be a useful tool in the diagnosis of mature B-cell neoplasms. More studies are needed to validate Ki-67 assessment with flow cytometry immunophenotyping.
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Remnant, Lucy, Natalia Y. Kochanova, Caitlin Reid, Fernanda Cisneros-Soberanis, and William C. Earnshaw. "The intrinsically disorderly story of Ki-67." Open Biology 11, no. 8 (2021): 210120. http://dx.doi.org/10.1098/rsob.210120.
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Ki-67 is one of the most famous marker proteins used by histologists to identify proliferating cells. Indeed, over 30 000 articles referring to Ki-67 are listed on PubMed. Here, we review some of the current literature regarding the protein. Despite its clinical importance, our knowledge of the molecular biology and biochemistry of Ki-67 is far from complete, and its exact molecular function(s) remain enigmatic. Furthermore, reports describing Ki-67 function are often contradictory, and it has only recently become clear that this proliferation marker is itself dispensable for cell proliferation. We discuss the unusual organization of the protein and its mRNA and how they relate to various models for its function. In particular, we focus on ways in which the intrinsically disordered structure of Ki-67 might aid in the assembly of the still-mysterious mitotic chromosome periphery compartment by controlling liquid–liquid phase separation of nucleolar proteins and RNAs.
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Panjkovic, Milana, and Tatjana Ivkovic-Kapicl. "Ki-67 expression in squamous intraepithelial lesions of the uterine cervix." Archive of Oncology 14, no. 1-2 (2006): 23–25. http://dx.doi.org/10.2298/aoo0602023p.
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BACKGROUND: Uncontrolled cell proliferation and malignant transformation are the basic elements in the development of malignant disease including cervical cancer and its precursors. The aim of this study was to investigate the proliferative activity by using Ki-67 proliferative marker according to CIN grade. METHODS: We used immunohistochemical methods to study the expression of the proliferative marker Ki-67 in the specimens of 5 patients with normal cervical epithelium, 7 with CIN1, 13 with CIN2, and 25 patients with CIN3 grade of the cervical intraepithelial lesions. RESULTS: All cases with normal cervical epithelium and all those with CIN1 changes had negative proliferative Ki-67 index. Ki-67 positive proliferative index was found in 5 (38.46%) and 17 (68%) of patients with CIN2 and CIN3 changes respectively. There was a clear trend for increasing number of cases with positive Ki-67 index with increasing CIN grade. High significant difference of Ki-67 expression was found between patients with CIN1 and CIN2 lesions (t=2.9; p<0.01). Ki-67 positive cells were distributed only in the lower third of the epithelial layer in CIN1 cases. Seven (53.8%) and 13 (52%) of patients with CIN2 and CIN3 changes respectively, had Ki-67 positive cells in the lower and middle third of the epithelial layer, while 3 (23.1%) and 10 (40%) of cases with the same dysplastic changes had Ki-67 positive cells distributed in lower, middle and upper third of the epithelium. Difference of the Ki-67 positive cells distribution was highly significant between patient with CIN1 and CIN2 epithelial changes. CONCLUSION: The present study shows that there is statistically significant relation between proliferative activity, distribution of Ki-67 positive cells, and CIN grade. Ki-67 antigen could be a tool to identify women who are at higher risk for progression and/or recurrence of cervical squamous precancerous lesions.
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Wang, Xuanzhi, Mingwu Li, Xiaofeng Jiang, Fei Wang, Shiying Ling, and Chaoshi Niu. "Prediction of Higher Ki-67 Index in Pituitary Adenomas by Pre- and Intra-Operative Clinical Characteristics." Brain Sciences 12, no. 8 (2022): 1002. http://dx.doi.org/10.3390/brainsci12081002.
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Objective: The Ki-67 index is an indicator of the active proliferation and aggressive behavior of pituitary adenomas (PAs). Appropriate pre- and intra-operatives of the Ki-67 index can help surgeons develop better and more personalized treatment strategies for patients with PAs. This study aimed to investigate the influence factors for predicting the Ki-67 index in PAs. Methods: Data of 178 patients with PAs confirmed by pathology were retrospectively analyzed. According to the Ki-67 index, the patients were divided into the Ki-67 < 3% and Ki-67 ≥ 3% cohorts. Patient data, including age, sex, postoperative immunohistochemical pituitary hormone positive index, Knosp grade, tumor breaking through the sellar floor, rich blood supply to the tumor, tumor located inside the sella, erosion of the dorsum sellae bone, and pituitary-specific transcription factor, were collected. A univariate logistic analysis was used to evaluate the influence factors for a high Ki-67 index. Multiple regression and receiver operating characteristic (ROC) curve were used to analyze the factors with p < 0.05. The mutant status of Ki-67 index was predicted by nomogram. Results: Multivariate regression analysis showed that rich blood supply to the tumor and erosion of the dorsum sellae bone were independent risk factors for the Ki-67 proliferation index. The ROC curves demonstrated that age, rich blood supply to the tumor, and erosion of the dorsum sellae bone can predict the occurrence of a high Ki-67 index. Together, the three risk factors provide a stronger ability to predict the Ki-67 index. The nomogram was developed and validated. Conclusion: Age, rich blood supply to the tumor, and erosion of the dorsum sellae bone are influencing factors for predicting the Ki-67 index. Suitable nomogram prediction models were developed and validated, and there is potential for personalized treatment for PA patients.
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Schlüter, C., M. Duchrow, C. Wohlenberg, et al. "The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins." Journal of Cell Biology 123, no. 3 (1993): 513–22. http://dx.doi.org/10.1083/jcb.123.3.513.
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The antigen defined by mAb Ki-67 is a human nuclear protein the expression of which is strictly associated with cell proliferation and which is widely used in routine pathology as a "proliferation marker" to measure the growth fraction of cells in human tumors. Ki-67 detects a double band with apparent molecular weights of 395 and 345 kD in immunoblots of proteins from proliferating cells. We cloned and sequenced the full length cDNA, identified two differentially spliced isoforms of mRNA with open reading frames of 9,768 and 8,688 bp encoding for this cell proliferation-associated protein with calculated molecular weights of 358,761 D and 319,508 D, respectively. New mAbs against a bacterially expressed part and a synthetic polypeptide deduced from the isolated cDNA react with the native Ki-67 antigen, thus providing a circle of evidence that we have cloned the authentic Ki-67 antigen cDNA. The central part of the Ki-67 antigen cDNA contains a large 6,845-bp exon with 16 tandemly repeated 366-bp elements, the "Ki-67 repeats", each including a highly conserved new motif of 66 bp, the "Ki-67 motif", which encodes for the epitope detected by Ki-67. Computer analysis of the nucleic acid and the deduced amino acid sequence of the Ki-67 antigen confirmed that the cDNA encodes for a nuclear and short-lived protein without any significant homology to known sequences. Ki-67 antigen-specific antisense oligonucleotides inhibit the proliferation of IM-9 cell line cells, indicating that the Ki-67 antigen may be an absolute requirement for maintaining cell proliferation. We conclude that the Ki-67 antigen defines a new category of cell cycle-associated nuclear nonhistone proteins.
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Kang, Young-Joon, Han-Byoel Lee, Yun Gyoung Kim, et al. "Ki-67 Expression is a Significant Prognostic Factor Only When Progesterone Receptor Expression is Low in Estrogen Receptor-Positive and HER2-Negative Early Breast Cancer." Journal of Oncology 2019 (December 28, 2019): 1–8. http://dx.doi.org/10.1155/2019/7386734.
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Objective. While the value of Ki-67 has been recognized in breast cancer, controversy also exists. The goal of this study is to show the prognostic value of Ki-67 according to progesterone receptor (PgR) expression in patients who have estrogen receptor- (ER-) positive, human epidermal growth factor receptor 2- (HER2-) negative early breast cancer. Methods. The records of nonmetastatic invasive breast cancer patients who underwent surgery at a single institution between 2009 and 2012 were reviewed. Primary end point was recurrence-free survival (RFS), and secondary end point was overall survival (OS). Ki-67 and PgR were assessed with immunohistochemistry for the tumor after surgery. Results. A total of 1848 patients were enrolled in this study. 223 (12%) patients had high (≥10%) Ki-67, and 1625 (88%) had low Ki-67 expression. Significantly worse RFS and OS were observed in the high vs. low Ki-67 expression only when the PgR was low (<20%) (p<0.001 and 0.005, respectively, for RFS and OS). There was no significant difference in RFS and OS according to Ki-67 when the PgR was high (p=0.120 and 0.076). RFS of four groups according to high/low Ki-67 and PgR expression was compared. The low PgR and high Ki-67 expression group showed worst outcome among them (p<0.001). In a multivariate analysis, high Ki-67 was an independent prognostic factor when the PgR was low (HR 3.05; 95% CI 1.50–6.19; p=0.002). Conclusions. Ki-67 had a value as a prognostic factor only under low PgR expression level in early breast cancer. PgR should be considered in evaluating the prognosis of breast cancer patients using Ki-67.
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Finkelman, Brian S., Huina Zhang, David G. Hicks, and Bradley M. Turner. "The Evolution of Ki-67 and Breast Carcinoma: Past Observations, Present Directions, and Future Considerations." Cancers 15, no. 3 (2023): 808. http://dx.doi.org/10.3390/cancers15030808.
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The 1983 discovery of a mouse monoclonal antibody—the Ki-67 antibody—that recognized a nuclear antigen present only in proliferating cells represented a seminal discovery for the pathologic assessment of cellular proliferation in breast cancer and other solid tumors. Cellular proliferation is a central determinant of prognosis and response to cytotoxic chemotherapy in patients with breast cancer, and since the discovery of the Ki-67 antibody, Ki-67 has evolved as an important biomarker with both prognostic and predictive potential in breast cancer. Although there is universal recognition among the international guideline recommendations of the value of Ki-67 in breast cancer, recommendations for the actual use of Ki-67 assays in the prognostic and predictive evaluation of breast cancer remain mixed, primarily due to the lack of assay standardization and inconsistent inter-observer and inter-laboratory reproducibility. The treatment of high-risk ER-positive/human epidermal growth factor receptor-2 (HER2) negative breast cancer with the recently FDA-approved drug abemaciclib relies on a quantitative assessment of Ki-67 expression in the treatment decision algorithm. This further reinforces the urgent need for standardization of Ki-67 antibody selection and staining interpretation, which will hopefully lead to multidisciplinary consensus on the use of Ki-67 as a prognostic and predictive marker in breast cancer. The goals of this review are to highlight the historical evolution of Ki-67 in breast cancer, summarize the present literature on Ki-67 in breast cancer, and discuss the evolving literature on the use of Ki-67 as a companion diagnostic biomarker in breast cancer, with consideration for the necessary changes required across pathology practices to help increase the reliability and widespread adoption of Ki-67 as a prognostic and predictive marker for breast cancer in clinical practice.
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Asri, Aswiyanti, Pamelia Mayorita, and Daan Khambri. "HUBUNGAN EKSPRESI Ki-67 DENGAN KARAKTERISTIK HISTOPATOLOGIK PADA KANKER PAYUDARA TRIPEL NEGATIF." Majalah Kedokteran Andalas 38, no. 3 (2015): 165. http://dx.doi.org/10.22338/mka.v38.i3.p165-172.2015.
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AbstrakKanker payudara triple negative mempunyai prognosis paling buruk. Ki-67, derajat diferensiasi dan invasi limfovaskular (LVI) adalah parameter prognostik patomolekuler, dimana Ki-67 juga dipakai sebagai prediktor respon terapi. Penelitian ini bertujuan untuk mengetahui hubungan derajat diferensiasi dan LVI dengan ekspresi Ki-67 pada kanker payudara tripel negatif. Sembilan belas kasus kanker payudara tripel negatif dikumpulkan dan direview ulang derajat diferensiasi dan LVI. Hasil pemeriksaan Ki-67 dikelompokkan dimana ≤10 % sampai 29 % ekspresi rendah-sedang; dan >30% ekspresi tinggi. Hubungan antara ekspresi Ki-67 dengan derajat diferensiasi dan invasi limfovaskular dianalisis menggunakan Chi Square. Dari 19 kasus kanker payudara tripel negatif, 52,6 % kasus mempunyai derajat diferensiasi tinggi dan sisanya derajat diferensiasi rendah. Invasi limfovaskular ditemukan positif pada 68,4% kasus. Ekspresi Ki-67 yang tinggi hanya ditemukan pada 1 kasus. Uji statistik antara ekspresi Ki-67 dengan derajat diferensiasi maupun dengan invasi limfovaskular tidak ditemukan hubungan yang bermakna. Tidak ditemukan korelasi antara ekspresi Ki-67 dengan derajat diferensiasi dan invasi limfovaskular pada kanker payudara tripel negatif.AbstractTriple negative breast cancer is one of the breast cancer with poorest prognosis. Ki- 67, grade and lymphovascular invasion are the prognostic pathomolecular parameter, and also used as a predictor of response to therapy. The objective of this study was to identify the relationship between Ki-67 expression with grade and lymphovascular invasion in triple negative breast cancer. We found 19 cases of triple negative breast cancer,and performed slide review for grade and lymphovascular invasion. The results of Ki-67 expression were classifiy as low – intermediate (< 10 % - 29%) and high (> 30%). We use Chi Square test to assest the relationship between variables. Of 19 triple negative breast cancer cases, 52,6 % of cases were found to have high histopathological grade. Positive lymphovascular invasion was seen in 68,4% cases. Only one case was found with high expression of Ki-67. There were no correlation between Ki-67 expression with histopathological grade and lymphovascular invasion on triple negative breast cancer. There were no significant relationship between Ki-67 expression with grade and lymphovascular invasion on triple negative breast cancer.
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Kim, Kwanil, Kyunghee Lee, and Heungkyu Park. "Value of Ki-67 in prediction of response to neoadjuvant chemotherapy in breast cancer." Journal of Clinical Oncology 31, no. 15_suppl (2013): e12025-e12025. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e12025.
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e12025 Background: The expression of the human Ki-67 protein has been described as being associated with cellular proliferative activity. The objective of this study is to assess the potential value of Ki-67 for the prediction of therapeutic response after neoadjuvant chemotherapy in breast cancer. Methods: Sixty-eight patients who underwent anthracyclin based neoadjuvant chemotherapy between 2007 and 2012 were included for this study. The chemotherapy response was evaluated by comparing the pre- and post-neoadjuvant chemotherapy tumor size on radiologic imaging study with the tumor size at pathologic specimens according to RECIST (response evaluation criteria in solid tumors) version 1.1. We analyzed immunohistochemical(ER, PR, HER2, Ki-67, p53) profiles from both pre-neoadjuvant core biopsy and postoperative specimens to find their correlations with chemotherapy response. Results: Ten patients(14.7%) achieved pathologic complete response(pCR), 38 patients(55.9%) had pathologic partial response(pPR) and 20 patients(29.4%) had pathologic stable disease(pSD). The mean Ki-67 value of tumors with pCR was 61.0%, the Ki-67 value of tumors with pPR was 35.9%, and the Ki-67 value of tumors with pSD was 21.0%(p = 0.013). The analysis of Ki-67 values of the patients also showed that 25% of Ki-67 level is a reasonable cut-off value for defining higher Ki-67 level. In subgroup analysis, the higher Ki-67 level was significant factor of the response to neoadjuvant chemotherapy, especially in ER negative patients(p = 0.009) and HER2 negative patients(p = 0.009). In addition, the analaysis of response group showed that ER negative(p = 0.027), HER2 positive(p = 0.048), and higher Ki-67 level(p = 0.002) were predictive indicators of complete response. Conclusions: The higher Ki-67 level of breast cancer tissue may effectively indicate the higher response rate to chemotherapy and also the higher complete response rate. The results of our study suggest that the Ki-67 value before neoadjuvant chemotherapy is a predictive factor for the response to neoadjuvant chemotherapy. Moreover, the Ki-67 is a predictive factor of the pathologic complete response especially in patients with ER negative or HER2 positive.
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Pyo, Jung-Soo, and Nae Yu Kim. "Meta-Analysis of Prognostic Role of Ki-67 Labeling Index in Gastric Carcinoma." International Journal of Biological Markers 32, no. 4 (2017): 447–53. http://dx.doi.org/10.5301/ijbm.5000277.
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Background This meta-analysis aimed to elucidate the prognostic role of the Ki-67 labeling index (LI) in gastric cancer (GC). Methods The current study included 3,615 GC patients in 20 eligible studies, and evaluated the prognostic role of Ki-67 LI in GC. Subgroup analysis was conducted based on depth of invasion and cutoff value for high Ki-67 LI. Results A high Ki-67 LI correlated significantly with worse survival (hazard ratio [HR] = 1.214, 95% confidence interval [CI], 1.004-1.468). However, there was no significant correlation between high Ki-67 LI and worse survival in advanced GC (HR = 1.252, 95% CI, 0.801-1.956). The subgroup with cutoff value ≤25% showed a significant correlation with worse survival, but this was not seen in the subgroup with cutoff >25% (HR = 1.433, 95% CI, 1.094-1.876 vs. HR = 1.005, 95% CI, 0.801-1.262). In addition, in the 10% < Ki-67 LI ≤ 20% range, there was a significant correlation between high Ki-67 LI and worse overall survival (HR = 1.931, 95% CI, 1.013-3.310). Conclusions A high Ki-67 LI correlated significantly with a worse prognosis in GC patients. Further cumulative studies for the optimal cutoff value for high Ki-67 LI are needed before application in clinical practice.