Artículos de revistas: "Grade de Gleason"

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Gupta, Sajjan, Ishan Dubey, Vandana Agarwal y Shalakha Agarwal. "New perspectives in modified Gleason’s grading for prostatic cancer and its comparison with original Gleason’s". International Journal of Research in Medical Sciences 7, n.º 2 (25 de enero de 2019): 400. http://dx.doi.org/10.18203/2320-6012.ijrms20190342.

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Background: The Gleason score is the most widely accepted histopathological grading system for prostate cancer since decade despite having many deficiency that can potentially impact patient health care. So ISUP agreed on developing a system of prognostic grade groups from I-V. Aim and objective was to study the new perspectives of modified Gleason’s grading and to compare it with original Gleason’s System with focus on the prognostic significance of the modifications.Methods: A retrospective study of 60 patients, who underwent TURP and Sextant biopsy and diagnosed as prostatic carcinoma in our institute were included in this study. Laboratory requisition forms with clinical history, PSA levels and histopathology reports of these patients were reviewed and graded accordingly to the newer gleasons. New Gleason grade includes five distinct Grade Groups based on the modified Gleason score groups. Grade Group 1 = Gleason score ≤6, Grade Group 2 = Gleason score 3 + 4 = 7, Grade Group 3 = Gleason score 4 + 3 = 7, Grade Group 4 = Gleason score 8, Grade Group 5 = Gleason scores 9 and 10 were assigned. The change in the grading system is tabulated and compared separately.Results: Patients age ranged from 55-80 years. The number of cases were 3,12,15,19 and 11 categorized under grade group I, grade group II, grade group III, grade group IV, grade group V cancer respectively according to modified gleason grading.Conclusions: Modified Gleason is a simplified grading system which may reduce over treatment of indolent prostate cancer. New gleasons grading clarifies the clinicians about the dilemma of gleason scores, offering an excellent prognostic stratification of this carcinoma.

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Tilki, D., F. Preisser, H. Huland, M. Graefen, F. Chun y P. Mandel. "Gleason grade grouping: The significance of primary Gleason 5 in patients with Gleason grade group 5". European Urology Supplements 18, n.º 1 (marzo de 2019): e2186. http://dx.doi.org/10.1016/s1569-9056(19)31579-9.

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Penney, Kathryn L., Meir J. Stampfer, Jaquelyn L. Jahn, Jennifer A. Sinnott, Richard Flavin, Jennifer R. Rider, Stephen Finn et al. "Gleason Grade Progression Is Uncommon". Cancer Research 73, n.º 16 (13 de agosto de 2013): 5163–68. http://dx.doi.org/10.1158/0008-5472.can-13-0427.

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Trock, Bruce J., Robert B. Jenkins, Jonathan W. Said, Samson Fine, Beatrice Knudsen, Helen L. Fedor, Bora Gurel, Tamara L. Lotan y Angelo M. De Marzo. "Chromosome 8 alterations and PTEN loss in Gleason grade 3 tumor to predict the presence of unsampled grade 4 tumor: Implications for active surveillance." Journal of Clinical Oncology 32, n.º 4_suppl (1 de febrero de 2014): 93. http://dx.doi.org/10.1200/jco.2014.32.4_suppl.93.

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93 Background: A key eligibility criterion in many active surveillance (AS) programs is that the biopsy exhibit only Gleason pattern 3 (G3) for a Gleason score of 6 or less. However, 25 to 35% of biopsy Gleason 6 is upgraded to Gleason 7 or higher in the prostatectomy (RP) specimen. Thus, there is a great need for biomarkers that, when measured on G3 tissue in a Gleason 6 biopsy, can predict the presence of unsampled higher grade tumor in the whole prostate. We evaluated PTEN loss by immunohistochemistry (IHC), and PTEN deletion, chromosome 8q (MYC) gain and 8p (LPL) loss by fluorescence in situ hybridization (FISH) for their ability to predict unsampled G4 tumor. Methods: A tissue microarray (TMA) was constructed of RP tissue from three groups of patients (n=50 per group) whose prostates exhibited only Gleason 3+3, only 3+4, or only 4+3 tumor, matched on age, year of RP, and race. In each patient, multiple cores sampled only from areas of G3 were evaluated for PTEN deletion by FISH, PTEN loss by IHC, and chromosome 8p/8q alterations by FISH. Biomarker results were compared between Gleason 6 versus 7 tumors using conditional logistic regression. Results: Patients underwent RP in 2001 to 2009, had median age 60, and median prostate-specific antigen 5.2; 63% of tumors were organ confined. In univariate analyses 8q gain (odds ratio OR=8.9, p<.0001), 8p loss (OR=6.9, p<.0001), PTEN loss by IHC (OR=5.7, p=.025), but not PTEN deletion by FISH (OR=1.5, p=.477) were significantly more common in G3 cores from Gleason 7 tumors than G3 cores from Gleason 6 tumors. In multivariable analyses, 8q gain (OR=6.2, p=.002) and 8p loss (OR=5.2, p=.0002) remained highly significant. At least one high risk biomarker (8q gain, 8p loss, PTEN loss, or PTEN deletion) was found in 35.7% of Gleason 3+3 versus 77.1% of Gleason 3+4 versus 91.3% of Gleason 4+3 tumors, p<.0001. Adjustment for confounding factors did not change the results. Conclusions: Chromosomal 8q gains (MYC), 8p loss (LPL), and PTEN loss measured in Gleason G3 TMA cores strongly differentiate whether the core comes from Gleason 6 or Gleason 7 tumor. If validated in biopsy Gleason 6 cores to predict prostatectomy Gleason 7 tumor these biomarkers could facilitate safe selection of men for active surveillance.

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Kristiana, Tjandra, I. Gusti Ayu Sri Mahendra Dewi, Luh Putu Iin Indrayani Maker, Herman Saputra, Ni Putu Sriwidyani y I. Made Muliarta. "Loss of Phosphatase and Tensin Homologue (PTEN) Expression Associated with Higher Risk Grade Group Gleason Prostate Adenocarcinoma in Sanglah Hospital Denpasar". Indonesian Journal of Cancer 13, n.º 4 (27 de diciembre de 2019): 127. http://dx.doi.org/10.33371/ijoc.v13i4.680.

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Background: Prostate cancer is the second most common malignancy in men and the fifth most common cause of death worldwide. In Asia, 59.3% of patients come for the advanced stage treatment. PTEN inactivation is identified in about 20% of primary prostate tumors in radical prostatectomy and the loss of PTEN is associated with poor clinical and pathological outcomes. The purpose of this study is to prove that there is an association between PTEN expression and risk grade group Gleason prostate adenocarcinoma in Sanglah Public Hospital, Denpasar.Methods: This is a cross-sectional study. The sample size of this study was 35 paraffin blocks. These samples were selected by proportional stratified random sampling from hematoxylin-eosin preparation. Prostate adenocarcinoma was regrouped into 3 categories based on NCCN risk stratification: low risk grade group Gleason (Gleason score ≤ 6), intermediate risk grade group Gleason (Gleason score 7), and high-risk grade group Gleason (Gleason score 8–10). Immunohistochemistry examination of PTEN was performed and the expression was evaluated by scoring method. The data were analyzed by Chi-square and logistic regression.Results: The analysis result showed that there is an association between PTEN expression and risk grade group Gleason that is statistically significant. The loss of PTEN expression associated with higher risk grade group Gleason is of the higher proportion with p=0.001; PR 3.339; 95% CI: 1.296–8.599, but there is no association between the proportion loss of PTEN expression heterogeneously or homogeneously and the risk grade group Gleason with p=0.742; PR 0.663; 95% CI: 0.179–2.457.Conclusions: This study has proved that PTEN expression is associated with higher risk grade group Gleason prostate adenocarcinoma.

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Feuerstein, Michael, Tipu Nazeer y Badar M. Mian. "CORRELATION BETWEEN GLEASON GRADE AT THE SURGICAL MARGIN WITH THE PRIMARY GLEASON GRADE AND BIOCHEMICAL FAILURE". Journal of Urology 179, n.º 4S (abril de 2008): 653. http://dx.doi.org/10.1016/s0022-5347(08)61909-6.

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Penney, Kathryn L., Jennifer A. Sinnott, Katja Fall, Yudi Pawitan, Yujin Hoshida, Peter Kraft, Jennifer R. Stark et al. "mRNA Expression Signature of Gleason Grade Predicts Lethal Prostate Cancer". Journal of Clinical Oncology 29, n.º 17 (10 de junio de 2011): 2391–96. http://dx.doi.org/10.1200/jco.2010.32.6421.

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Purpose Prostate-specific antigen screening has led to enormous overtreatment of prostate cancer because of the inability to distinguish potentially lethal disease at diagnosis. We reasoned that by identifying an mRNA signature of Gleason grade, the best predictor of prognosis, we could improve prediction of lethal disease among men with moderate Gleason 7 tumors, the most common grade, and the most indeterminate in terms of prognosis. Patients and Methods Using the complementary DNA–mediated annealing, selection, extension, and ligation assay, we measured the mRNA expression of 6,100 genes in prostate tumor tissue in the Swedish Watchful Waiting cohort (n = 358) and Physicians' Health Study (PHS; n = 109). We developed an mRNA signature of Gleason grade comparing individuals with Gleason ≤ 6 to those with Gleason ≥ 8 tumors and applied the model among patients with Gleason 7 to discriminate lethal cases. Results We built a 157-gene signature using the Swedish data that predicted Gleason with low misclassification (area under the curve [AUC] = 0.91); when this signature was tested in the PHS, the discriminatory ability remained high (AUC = 0.94). In men with Gleason 7 tumors, who were excluded from the model building, the signature significantly improved the prediction of lethal disease beyond knowing whether the Gleason score was 4 + 3 or 3 + 4 (P = .006). Conclusion Our expression signature and the genes identified may improve our understanding of the de-differentiation process of prostate tumors. Additionally, the signature may have clinical applications among men with Gleason 7, by further estimating their risk of lethal prostate cancer and thereby guiding therapy decisions to improve outcomes and reduce overtreatment.

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Pudasaini, Sujata y Neeraj Subedi. "Understanding the gleason grading system and its changes". Journal of Pathology of Nepal 9, n.º 2 (29 de septiembre de 2019): 1580–85. http://dx.doi.org/10.3126/jpn.v9i2.25723.

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Gleason Grading System is the most widely used grading system used for prostatic carcinoma. The five basic grade patterns are used to generate a histologic score, which can range from 2 to 10 (including primary and secondary patterns). The original Gleason Grading System was used to grade acinar adenocarcinoma based on architectural features and it has been correlated with excellent clinical outcomes. Since 1960s, after the discovery of the original Gleason Grading System, a modified version of the Gleason Grading System was introduced in the International Society of Urological Pathology 2005 which came up with many changes including elimination of Gleason pattern 1. The ISUP 2005 was further updated in 2014 to provide more accurate stratification of prostatic carcinoma. The new Gleason Grade Group 1 to 5 has been introduced and it has little resemblance to the original Gleason system. This Gleason Grade Group has been accepted by the 2016 World Health Organization classification of tumors of the prostate. For a needle biopsy, high grade component of any quantity should be included in the Gleason score as it indicates a high probability of finding significant high grade tumor in the prostate. By understanding the principles and practice of this grading system, the pathology report has to clearly indicate which system is adopted in the reporting. This review discusses GGS and its recent development focusing on major changes over the years that led to the new Grade Group system proposed by the 2014 ISUP consensus.

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VanderWeele, David James, Christopher D. Brown, Robert L. Grossman, Jerome B. Taxy, Walter Michael Stadler y Kevin P. White. "The genomic relationship among matched prostate cancer foci." Journal of Clinical Oncology 31, n.º 15_suppl (20 de mayo de 2013): 5028. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.5028.

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5028 Background: Cancer management is influenced by how one views progression and how one calculates the risk of metastases and death. For prostate cancer, this is based largely on histologic appearance, or Gleason score. Cancers with a Gleason score of 6 exhibit indolent behavior and are often considered low risk. Despite recommendations supporting active surveillance for Gleason 6 prostate cancer, the vast majority of American patients receive aggressive local therapy, in part based on a presumption that low grade cancer progresses to high grade, lethal disease. Methods: To assess the genomic relationship between low and high grade disease, laser capture microdissection was used to isolate concurrent cancer foci from prostates with multifocal disease, and somatic mutations were identified using exome sequencing. The relationship between a Gleason 6 focus and a concurrent Gleason 8 or higher focus was determined for four subjects, and a lymph node metastasis was examined for two of those subjects. Results: We obtained an average of 41-fold median coverage of the exome, with an average high confidence mutation rate of 0.8/Mb. Seventy of 79 (0.886) high confidence somatic mutations in low grade disease were private to the low grade foci. For the cases for which a metastatic focus was available, 15 of 80 (0.188) high confidence somatic mutations in the high grade focus were private. Seven of the 80 (0.088) were shared with low grade foci, and 65 (0.813) were shared with metastatic foci. Conclusions: The pattern of shared versus private mutations is consistent with early divergence between Gleason 6 and Gleason 8 or 9 disease, and late divergence between Gleason 8 disease and lymph node metastases. These data support a model of parallel evolution of lower and higher Gleason score disease, rather than progression from Gleason 6 to higher Gleason scores.

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Larasati, Putri Ajeng ayu. "KORELASI ANTARA EKSPRESI Her-2 DAN Ki-67 DENGAN GLEASON GRADE GROUP PADA ADENOKARSINOMA ASINAR PROSTAT". Jurnal Kedokteran RAFLESIA 5, n.º 1 (31 de octubre de 2019): 39–52. http://dx.doi.org/10.33369/juke.v5i1.9125.

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Latar Belakang : Menurut Database GLOBOCAN 2012, kanker prostat merupakan penyebab utama kelima kematian pada pria.(1) Pemahaman tentang peran onkogen dan tumor suppressor genes mendominasi penelitian tentang biologi kanker saat ini dan berpotensi menghasilkan target terapi kanker terbaru. Salah satu perannya pada adenokarsinoma prostat yang masih belum jelas ialah Her-2 dan Ki-67. Perbedaan ekspresi profil molekular Her-2 dan Ki-67 yang diklasifikasikan berdasarkan Gleason grading system terbaru yaitu Grade group diharapkan membantu penentuan prognosis dan manajemen terapi penyakit pada kanker prostat.Tujuan : Tujuan dari penelitian ini adalah untuk mengetahui korelasi antara ekspresi Her-2 dan Ki-67 dengan Gleason Grade group adenokarsinoma asinar prostat.Metode: Merupakan penelitian observatif analitik dengan desain cross-sectional menggunakan 31 blok parafin yang terfiksasi formalin dari laboratorium Patologi Anatomik RSUP dr. Kariadi, dengan diagnosis adenokarsinoma asinar prostat kemudian diklasifikasikan menurut kelompok prognostik WHO / ISUP Gleason (Gleason Grade group 1 - 5). Pemeriksaan imunohistokimia dilakukan dengan menggunakan antibodi Her-2 dan Ki-67. Analisa hasil menggunakan uji Spearmans dan uji Kruskal WallisHasil : 31 kasus yang termasuk dalam kriteria inklusi pada penelitian ini, hampir separuhnya (41.94%) termasuk ke dalam Gleason grade group 5. Ekspresi Her-2 positif (+1, +2, +3) hampir didapatkan pada seluruh sampel (90,22%), dengan Her-2 +3 sebagian besar didapatkan pada grade group 5 (71,43%). Ekspresi Ki-67 positif (+1, +2, +3) didapatkan pada seluruh sampel, dengan Ki-67 +3 (>5%) pada Gleason grade group 5 didapatkan sejumlah 5 sampel (38,46%). Pada analisa data dengan uji Spearmans disimpulkan bahwa terdapat korelasi positif antara ekspresi Her-2 dan Ki-67 dengan Gleason Grade group. Pada uji Kruskal Wallis didapatkan perbedaan bermakna antara ekspresi Ki-67 dengan Gleason Grade group.Kesimpulan: Analisa ekspresi Her-2 dan Ki-67 melalui pemeriksaan imunohistokimia dengan klasifikasi terbaru Gleason Grade group dapat menjadi salah satu parameter prognosis dan manajemen terapi pada adenokarsinoma asinar prostat.Kata kunci : Adenokarsinoma asinar prostat, Her-2, Ki-67, Gleason Grade group

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Leapman, Michael S., Janet E. Cowan, Gray Roberge, Mohamed M. Eltemamy, Jeff Simko, Peter Carroll y Matthew R. Cooperberg. "External validation of a prognostic Gleason grade classification system." Journal of Clinical Oncology 34, n.º 2_suppl (10 de enero de 2016): 123. http://dx.doi.org/10.1200/jco.2016.34.2_suppl.123.

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123 Background: We aimed to evaluate a recently proposed prognostic Gleason grading system among two distinct cohorts of men receiving treatment for localized PCa with extended clinical follow. Methods: We identified patients receiving treatment with radical prostatectomy (RP) in two settings: an academic referral center and the multi-center Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) registry. We examined the independent prognostic ability of the proposed grade groups (3+3; 3+4; 4+3; 4+4; 9-10), adjusted for significant clinical and pathological characteristics, on disease recurrence, defined as two consecutive PSA values ≥ 0.2 ng/mL or receipt of salvage treatment, using Cox proportional hazards models. Adjusted pairwise comparisons were made between grade groups. Distant disease endpoints including metastatic progression and prostate cancer specific mortality (PCSM) were similarly evaluated within the CaPSURE cohort. Results: We identified 1,734 men receiving treatment at UCSF with immediate RP with pathologic assessment consistent with the 2005 ISUP modification, and 4,564 men within the CaPSURE database. Median follow up within the UCSF cohort was 33 months (interquartile range, IQR 16-58) and 91 months (IQR 50-135) within CaPSURE. Relative to Gleason grade 3+3, all prognostic Gleason grade groups were independently associated with risk of recurrence among the UCSF cohort (all p < 0.01). Adjusted pairwise comparisons of biopsy and pathologic Gleason groups, except 4+3 versus 4+4, also were statistically significant. Among the CaPSURE cohort, biopsy and pathologic prognostic Gleason grade groups were independently associated with risk of recurrence, metastatic progression and PCSM, though pairwise distinctions between Gleason 4+3 and 4+4 and Gleason 4+4 versus 9-10 were not significant. This study was limited by the comparatively smaller proportion of men receiving radical prostatectomy for higher Gleason grade ( > 4+4) disease. Conclusions: A proposed prognostic Gleason classification system stratifies men according to the risk of recurrence and downstream endpoints. However, the discrimination of outcomes among higher grade disease appeared less robust.

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Montironi, Rodolfo, Liang Cheng, Marina Scarpelli y Antonio Lopez-Beltran. "From Gleason Grading System and High-grade Tertiary Patterns to Grade Groups and Integrated Quantitative Gleason Score". European Urology 73, n.º 5 (mayo de 2018): 684–86. http://dx.doi.org/10.1016/j.eururo.2017.01.038.

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Boehm, Katharina, Pierre Tennstedt, Burkhard Beyer, Jonas Schiffmann, Ann Beckmann, Uwe Michl, Dirk Beyersdorff et al. "Additional elastography-targeted biopsy improves the agreement between biopsy Gleason grade and Gleason grade at radical prostatectomy". World Journal of Urology 34, n.º 6 (19 de octubre de 2015): 805–10. http://dx.doi.org/10.1007/s00345-015-1714-1.

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Pierorazio, Phillip M., Patrick C. Walsh, Alan W. Partin y Jonathan I. Epstein. "Prognostic Gleason grade grouping: data based on the modified Gleason scoring system". BJU International 111, n.º 5 (6 de marzo de 2013): 753–60. http://dx.doi.org/10.1111/j.1464-410x.2012.11611.x.

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Freeman, Alex. "Prognostic Gleason grade grouping: data based on the modified Gleason scoring system". BJU International 111, n.º 5 (12 de abril de 2013): 691–92. http://dx.doi.org/10.1111/j.1464-410x.2012.11743.x.

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Bhattacharjee, Park, Kim, Prakash, Madusanka, So, Cho y Choi. "Quantitative Analysis of Benign and Malignant Tumors in Histopathology: Predicting Prostate Cancer Grading Using SVM". Applied Sciences 9, n.º 15 (24 de julio de 2019): 2969. http://dx.doi.org/10.3390/app9152969.

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An adenocarcinoma is a type of malignant cancerous tissue that forms from a glandular structure in epithelial tissue. Analyzed stained microscopic biopsy images were used to perform image manipulation and extract significant features for support vector machine (SVM) classification, to predict the Gleason grading of prostate cancer (PCa) based on the morphological features of the cell nucleus and lumen. Histopathology biopsy tissue images were used and categorized into four Gleason grade groups, namely Grade 3, Grade 4, Grade 5, and benign. The first three grades are considered malignant. K-means and watershed algorithms were used for color-based segmentation and separation of overlapping cell nuclei, respectively. In total, 400 images, divided equally among the four groups, were collected for SVM classification. To classify the proposed morphological features, SVM classification based on binary learning was performed using linear and Gaussian classifiers. The prediction model yielded an accuracy of 88.7% for malignant vs. benign, 85.0% for Grade 3 vs. Grade 4, 5, and 92.5% for Grade 4 vs. Grade 5. The SVM, based on biopsy-derived image features, consistently and accurately classified the Gleason grading of prostate cancer. All results are comparatively better than those reported in the literature.

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Yoo, Sun Mi, Lillian Werner, Mari Nakabayashi, Christopher Sweeney, Michelle S. Hirsch, Philip W. Kantoff y Mark M. Pomerantz. "Clinicopathologic features and clinical outcomes associated with Gleason upgrading from biopsy to radical prostatectomy." Journal of Clinical Oncology 31, n.º 15_suppl (20 de mayo de 2013): 5056. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.5056.

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5056 Background: Gleason score stratifies patients into prognostic categories and is critical in guiding treatment. Previous series indicate that ~25% of patients with low-grade (Gleason ≤6) disease on biopsy are upgraded to higher grade disease upon radical prostatectomy (RP). We sought to characterize the clinical and pathologic variables associated with upgrading and investigate its clinical implications. Methods: 1,469 prostate cancer patients underwent prostate biopsy and RP, were seen at Dana-Farber Cancer Institute/Brigham and Women’s Hospital (DFCI/BWH), and had tissue specimens reviewed by DFCI/BWH genitourinary pathologists between 1999-2011. Associations between Gleason upgrading and clinical and pathologic variables were assessed using Wilcoxon’s non-parametric test and Fisher’s exact tests. Log rank test was used to assess association between upgrading and time to biochemical recurrence (BCR). Results: Of 1,469 patients, 958 (65%) had biopsy Gleason 6 and 511 (35%) had biopsy Gleason 7. Among individuals with biopsy Gleason 6, 336 (35%) were upgraded to Gleason ≥7 upon RP (275 3+4 and 49 4+3) while 622 (65%) remained Gleason 6 at RP. Variables associated with increased risk of upgrading: greater PSA at diagnosis (p=1x10-4); age >58 (OR=1.62, p < 1x10-4); >1/3 positive biopsy cores (OR=2.1 for 33-50% compared to ≤33%, p < 1x10-4). In this study the number of cores biopsied was not associated with upgrading. Gleason upgrading was also associated with extraprostatic tissue involvement (OR=1.69, p=0.005). Patients upgraded from biopsy Gleason ≤6 to Gleason 7 on RP had a longer time to BCR than those with Gleason 7 on both biopsy and RP, but a shorter time to BCR than those who remained Gleason 6 on RP (adjusted hazard ratio 0.69, 95% CI 0.49-0.98, p=0.03). Conclusions: Gleason upgrading from low-grade to higher grade disease is associated with a higher PSA at diagnosis, older age at diagnosis, and a greater number of positive biopsy cores. Clinically, prostate cancers upgraded from Gleason ≤6 to Gleason 7 appear to behave differently than those who are not upgraded. These results could have implications in determining ideal candidates for active surveillance.

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VanderWeele, David James, Jerome B. Taxy, Walter Michael Stadler y Kevin P. White. "The molecular relationship among concurrent prostate cancer foci." Journal of Clinical Oncology 31, n.º 6_suppl (20 de febrero de 2013): 43. http://dx.doi.org/10.1200/jco.2013.31.6_suppl.43.

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43 Background: Prostate cancer management is influenced by how one views prostate cancer progression and how one calculates the risk of prostate cancer metastases and death. Currently this is based largely on histologic appearance, or Gleason score. Cancers with a Gleason score of 6 exhibit indolent behavior and are often considered low risk. NCCN guidelines endorse surveillance for many of these tumors. Malignancies with a Gleason score of 8-10 exhibit aggressive behavior and are considered high risk. Methods: Prostate cancer is usually multifocal, and these concurrent foci are often histologically distinct. In this study the molecular relationship between a Gleason 6 focus and a concurrent Gleason 8 or higher focus was determined for four subjects. In two subjects a lymph node metastasis was also examined. Laser capture microdissection was used to isolate these multiple matched foci, and somatic mutations were identified using exome sequencing. Results: We obtained an average of 40-fold median coverage of the exome, with an average high confidence mutation rate of 0.64/Mb, excluding nonsynonymous mutations. Seventy of 80 (0.875) high confidence somatic mutations in low grade disease were private to the low grade foci. For the cases for which a metastatic focus was available, 17 of 79 (0.215) high confidence somatic mutations in the high grade focus were private. Eight of the 79 (0.101) were shared with low grade foci, and 62 (0.785) were shared with metastatic foci. Conclusions: The pattern of shared versus private mutations was consistent with early divergence between Gleason 6 and Gleason 8 or 9 disease, and late divergence between Gleason 8 disease and lymph node metastases. These data support a model of parallel evolution of lower and higher Gleason score disease, rather than progression from Gleason 6 to higher Gleason scores.

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Greenwald, David Theodore, Alice Y. Wang, Jason Huang, Harpreet Wadhwa, Tony Nimeh, Justin J. Cohen y Paul Yonover. "Occurrence of pathologic stage T3 disease at radical prostatectomy with isup grade group 1 (Gleason 3+3=6) prostate cancer." Journal of Clinical Oncology 36, n.º 6_suppl (20 de febrero de 2018): 21. http://dx.doi.org/10.1200/jco.2018.36.6_suppl.21.

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21 Background: Treatment of ISUP Grade Group 1 (Gleason 3+3 = 6) disease continues to evolve in the modern era. We examined our surgical database to investigate patterns of behavior in this pathologic subset. Methods: We reviewed the results of 1127 consecutive radical prostatectomies performed by our surgeons from 2012−2015 at various community and academic medical centers in Chicagoland. Specifically, we examined the ISUP Grade Group 1 (Gleason 3+3 = 6) patients in our database, 314 patients overall. Results: A review of our database revealed that of ISUP Grade Group 1 (Gleason 3+3 = 6) patients (n = 314), only 3.82% had pT3 disease (11 patients stage pT3a and 1 stage pT3b). The only patient of these 12 to have lymphovascular invasion (LVI) was the singular pT3b patient. Overall, ISUP Grade Group 1 (Gleason 3+3 = 6) pT3 disease represents only 1.06% of all prostatectomies in our database. Conclusions: In our large prostatectomy cohort, ISUP Grade Group 1 (Gleason 3+3 = 6) prostate cancer was rarely associated with extra−prostatic extension (pT3) or lymphovascular invasion (LVI), suggesting that it has very low metastatic potential. These findings give further support to the trend of increased utilization of active surveillance for low risk prostate cancer.

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Hamzeh, Osama, Abedalrhman Alkhateeb, Julia Zhuoran Zheng, Srinath Kandalam, Crystal Leung, Govindaraja Atikukke, Dora Cavallo-Medved, Nallasivam Palanisamy y Luis Rueda. "A Hierarchical Machine Learning Model to Discover Gleason Grade-Specific Biomarkers in Prostate Cancer". Diagnostics 9, n.º 4 (11 de diciembre de 2019): 219. http://dx.doi.org/10.3390/diagnostics9040219.

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(1) Background:One of the most common cancers that affect North American men and men worldwide is prostate cancer. The Gleason score is a pathological grading system to examine the potential aggressiveness of the disease in the prostate tissue. Advancements in computing and next-generation sequencing technology now allow us to study the genomic profiles of patients in association with their different Gleason scores more accurately and effectively. (2) Methods: In this study, we used a novel machine learning method to analyse gene expression of prostate tumours with different Gleason scores, and identify potential genetic biomarkers for each Gleason group. We obtained a publicly-available RNA-Seq dataset of a cohort of 104 prostate cancer patients from the National Center for Biotechnology Information’s (NCBI) Gene Expression Omnibus (GEO) repository, and categorised patients based on their Gleason scores to create a hierarchy of disease progression. A hierarchical model with standard classifiers in different Gleason groups, also known as nodes, was developed to identify and predict nodes based on their mRNA or gene expression. In each node, patient samples were analysed via class imbalance and hybrid feature selection techniques to build the prediction model. The outcome from analysis of each node was a set of genes that could differentiate each Gleason group from the remaining groups. To validate the proposed method, the set of identified genes were used to classify a second dataset of 499 prostate cancer patients collected from cBioportal. (3) Results: The overall accuracy of applying this novel method to the first dataset was 93.3%; the method was further validated to have 87% accuracy using the second dataset. This method also identified genes that were not previously reported as potential biomarkers for specific Gleason groups. In particular, PIAS3 was identified as a potential biomarker for Gleason score 4 + 3 = 7, and UBE2V2 for Gleason score 6. (4) Insight: Previous reports show that the genes predicted by this newly proposed method strongly correlate with prostate cancer development and progression. Furthermore, pathway analysis shows that both PIAS3 and UBE2V2 share similar protein interaction pathways, the JAK/STAT signaling process.

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Ahdoot, Michael, Amir H. Lebastchi, Sandeep Gharam, Patrick H. Gomella, John Dibianco, Jonathan Bloom, Graham Hale et al. "MRI targeted biopsy dramatically increases detection of clinically significant prostate cancer while reducing the risk of indolent cancer detection." Journal of Clinical Oncology 37, n.º 7_suppl (1 de marzo de 2019): 108. http://dx.doi.org/10.1200/jco.2019.37.7_suppl.108.

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108 Background: MRI fusion prostate biopsy has been shown to improve detection of clinically significant prostate cancer, however the degree of this benefit is poorly characterized in large clinical trials. Methods: 1750 MRI targeted plus sextant biopsies were performed in 1742 male patients from 2007 to 2017. Patient demographics, PSA, prostate volume, primary and secondary Gleason scores, Johns Hopkins Grade Groups, number of MRI targeted lesions, number of cores obtained, and biopsy yield were recorded. Results: The patient population consisted of men averaging 62.9-year-old (36-86) with a mean PSA 9.6ng/mL, and prostate volume of 59.2 ml. A total of 804 cancers were detected on sextant biopsy and 839 were detected on MRI targeted biopsy. Relative to targeted biopsy, sextant biopsy detected only significantly more Gleason 6 disease (14% vs 21.5%, p < 0.0001) than targeted biopsy. Targeted biopsy detected more Gleason 7 (21% vs 16.6%, p = 0.0009) and Gleason 8-10 (13.4% vs 9.4%). Additionally, Gleason 7 sub-stratification demonstrated substantially more Gleason 4+3 detection in targeted group vs sextant biopsy (4% vs 0.5%, p < 0.0001). When stratified by Grade Group targeted biopsy detected 76% more Grade Group 3-5 cancers (p < 0.0001) and 17.7% less Gleason Group 1-2 cancers (p < 0.0001). Only 1.7% of Grade Group 3-5 cancers were detected on sextant biopsy alone, where as 15.7% of Grade Group 3-5 cancers were detected on targeted biopsy alone. Conclusions: MRI targeted biopsy significantly increases the likelihood of detecting clinically significant cancer and decreases the risk of indolent cancer detection. These finding strongly support the use of MRI targeted biopsy when possible.

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Shore, Neal, Steven A. Kaplan, Ronald Tutrone, Richard Levin, James Bailen, Alan Hay, Susan Kalota et al. "Prospective evaluation of fexapotide triflutate injection treatment of Grade Group 1 prostate cancer: 4-year results". World Journal of Urology 38, n.º 12 (22 de febrero de 2020): 3101–11. http://dx.doi.org/10.1007/s00345-020-03127-w.

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Abstract Purpose This study was undertaken to determine the safety and efficacy of fexapotide triflutate (FT) 2.5 mg and 15 mg for the treatment of Grade Group 1 prostate cancer. Methods Prospective randomized transrectal intraprostatic single injection FT 2.5 mg (n = 49), FT 15 mg (n = 48) and control active surveillance (AS) (n = 49) groups were compared in 146 patients at 28 U.S. sites, with elective AS crossover (n = 18) to FT after first follow-up biopsy at 45 days. Patients were followed for 5 years including biopsies (baseline, 45 days, and 18, 36, and 54 months thereafter), and urological evaluations with PSA every 6 months. Patients with Gleason grade increase or who elected surgical or radiotherapeutic intervention exited the study and were cumulatively included in the data analysis. Percentage of normal biopsies in baseline focus quadrant, tumor grades, and volumes; and outcomes including Gleason grade in entire prostate as well as treated prostate lobe, interventions associated with Gleason grade increase and total incidence of interventions were assessed. Results Significantly improved long-term clinical outcomes were found after 4-year follow-up, with percentages of patients progressing to interventions with and without Gleason grade increase significantly reduced by FT single treatment. Results in the FT 15-mg group were superior to the FT 2.5-mg dose group. There were no drug-related serious adverse events (SAEs). Conclusions FT showed statistically significant long-term efficacy in the treatment of Grade Group 1 patients regarding clinical and pathological progression. FT 15 mg showed superior results to FT 2.5 mg. There were no drug-related SAEs; FT injection was well tolerated.

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Koontz, Bridget F., Matvey Tsivian, Vladimir Mouraviev, Leon Sun, Zeljko Vujaskovic, Judd Moul y W. Robert Lee. "Impact of Primary Gleason Grade on Risk Stratification for Gleason Score 7 Prostate Cancers". International Journal of Radiation Oncology*Biology*Physics 82, n.º 1 (enero de 2012): 200–203. http://dx.doi.org/10.1016/j.ijrobp.2010.11.023.

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Zietman, Anthony, Joseph Smith, Eric Klein, Michael Droller, Prokar Dasgupta y James Catto. "Consensus Guidelines for Reporting Prostate Cancer Gleason Grade". Urology 93 (julio de 2016): 1. http://dx.doi.org/10.1016/j.urology.2016.03.002.

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Zietman, Anthony, Joseph Smith, Eric Klein, Michael Droller, Prokar Dasgupta y James Catto. "Consensus guidelines for reporting prostate cancer Gleason Grade". BJU International 117, n.º 6 (13 de mayo de 2016): 849. http://dx.doi.org/10.1111/bju.13470.

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Egevad, Lars, Hemamali Samaratunga, John R. Srigley, Brett Delahunt, Anthony Zietman, Joseph Smith, Eric Klein, Michael Droller, Prokar Dasgupta y James Catto. "Consensus guidelines for reporting prostate cancer Gleason Grade". BJU International 118, n.º 3 (14 de agosto de 2016): E1—E2. http://dx.doi.org/10.1111/bju.13596.

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Delahunt, Brett, Lars Egevad, Hemamali Samaratunga, Guido Martignoni, John N. Nacey y John R. Srigley. "Gleason and Fuhrman no longer make the grade". Histopathology 68, n.º 4 (16 de noviembre de 2015): 475–81. http://dx.doi.org/10.1111/his.12803.

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López, José I. "Gleason and Fuhrman no longer make the grade". Histopathology 69, n.º 2 (5 de abril de 2016): 340–41. http://dx.doi.org/10.1111/his.12946.

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Sfoungaristos, Stavros y Petros Perimenis. "Clinical and pathological variables that predict changes in tumour grade after radical prostatectomy in patients with prostate cancer". Canadian Urological Association Journal 7, n.º 1-2 (20 de febrero de 2013): 93. http://dx.doi.org/10.5489/cuaj.270.

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Introduction: Preoperative Gleason score is crucial, in combination with other preoperative parameters, in selecting the appropriate treatment for patients with clinically localized prostate cancer. The aim of the present study is to determine the clinical and pathological variables that can predict differences in Gleason score between biopsy and radical prostatectomy.Methods: We retrospectively analyzed the medical records of 302 patients who had a radical prostatectomy between January 2005 and September 2010. The association between grade changes and preoperative Gleason score, age, prostate volume, prostate-specific antigen (PSA), PSA density, number of biopsy cores, presence of prostatitis and high-grade prostatic intraepithelial neoplasia was analyzed. We also conducted a secondary analysis of the factors that influence upgrading in patients with preoperative Gleason score ≤6 (group 1) and downgrading in patients with Gleason score ≤7 (group 2).Results: No difference in Gleason score was noted in 44.3% of patients, while a downgrade was noted in 13.7% and upgrade in 42.1%. About 2/3 of patients with a Gleason score of ≤6 upgraded after radical prostatectomy. PSA density (p = 0.008) and prostate volume (p = 0.032) were significantly correlated with upgrade. No significant predictors were found for patients with Gleason score ≤7 who downgraded postoperatively.Conclusion: Smaller prostate volume and higher values of PSA density are predictors for upgrade in patients with biopsy Gleason score ≤6 and this should be considered when deferred treatment modalities are planned.

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Cheng, Liang, Michael O. Koch, Beth E. Juliar, Joanne K. Daggy, Richard S. Foster, Richard Bihrle y Thomas A. Gardner. "The Combined Percentage of Gleason Patterns 4 and 5 Is the Best Predictor of Cancer Progression After Radical Prostatectomy". Journal of Clinical Oncology 23, n.º 13 (1 de mayo de 2005): 2911–17. http://dx.doi.org/10.1200/jco.2005.03.018.

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Purpose Clinical outcome is variable in prostate cancer patients treated with radical prostatectomy. The Gleason histologic grade of prostatic adenocarcinoma is one of the strongest predictors of biologic aggressiveness of prostate cancer. We evaluated the significance of the relative proportion of high-grade cancer (Gleason patterns 4 and/or 5) in predicting cancer progression in prostate cancer patients treated with radical prostatectomy. Patients and Methods Radical prostatectomy specimens from 364 consecutive prostate cancer patients were totally embedded and whole mounted. Various clinical and pathologic characteristics were analyzed. All pathologic data, including Gleason grading variables, were collected prospectively. Results A multiple-factor analysis was performed that included the combined percentage of Gleason patterns 4 and 5, Gleason score, tumor stage, surgical margin status, preoperative prostate-specific antigen (PSA), extraprostatic extension, and total tumor volume. Using Cox regression analysis with bootstrap resampling for predictor selection, we identified the combined percentage of Gleason patterns 4 and 5 (P < .0001) and total tumor volume (P = .009) as significant predictors of PSA recurrence. Conclusion The combined percentage of Gleason patterns 4 and 5 is one of the most powerful predictors of patient outcome, and appears superior to conventional Gleason score in identifying patients at increased risk of disease progression. On the basis of our results, we recommend that the combined percentage of Gleason patterns 4 and 5 be evaluated in radical prostatectomy specimens. The amount of high-grade cancer in a prostatectomy specimen should be taken into account in therapeutic decision making and assessment of patient prognosis.

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Ghabili, Kamyar, Nathan Paulson, Jamil S. Syed, Cayce B. Nawaf, Ghazal Khajir, Darryl T. Martin, John Onofrey et al. "Doubling of Decipher Biopsy Genomic Score Is Related to Disease Reclassification on Subsequent Surveillance Biopsy but Not Adverse Features on Radical Prostatectomy". Case Reports in Urology 2021 (16 de marzo de 2021): 1–4. http://dx.doi.org/10.1155/2021/2687416.

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The utility of serial Decipher biopsy scores in a true active surveillance population is still unknown. In a man on active surveillance for low-risk prostate cancer, a doubling of the Decipher biopsy score within genomic low-risk category from first to the second biopsy related to biopsy reclassification to Gleason grade group 4 on the third biopsy. However, the final pathology at radical prostatectomy showed Gleason grade group 2 with an organ-confined disease. This case suggests that the genomic risk category of Decipher biopsy scores during active surveillance may be more informative than either the interval genomic score change or the biopsy Gleason grade group.

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Anwar, Shahgul, Robert A. Ambros, Timothy A. Jennings, Jeffrey S. Ross, Anton Beza, Badar Mian y Tipu Nazeer. "Expression of Cysteine Protease Protein 32 in Prostatic Adenocarcinoma Correlates With Tumor Grade". Archives of Pathology & Laboratory Medicine 128, n.º 6 (1 de junio de 2004): 649–52. http://dx.doi.org/10.5858/2004-128-649-eocppi.

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Abstract Context.—Controlled cell death is mediated by apoptosis-specific genes, tumor suppressor genes, and oncogenes. The caspase family is a group of at least 15 known cysteine proteases that serve as initiator and effector molecules of the apoptosis pathway. On activation, caspases cause cell shrinkage, condensation of chromatin, fragmentation of DNA, and the formation of blebs in the cytoplasmic membrane. Objectives.—The patterns of cysteine protease protein (CCP) 32 (caspase-3) expression have been determined in normal human tissues and a variety of tumors, and have been shown to correlate with the outcome in breast cancer and linked to resistance to chemotherapy in other tumors. This study was performed to determine whether CPP32 is expressed in prostatic adenocarcinoma and to define its relationship with outcome variables. Design.—Formalin-fixed, paraffin-embedded radical prostatectomy specimens from 211 patients with prostatic adenocarcinoma were evaluated for CPP32 expression by immunohistochemistry. Hematoxylin-eosin–stained slides were reviewed, and tumors were graded based on the Gleason grading system. Tumors were scored for CPP32 expression semiquantitatively, based on the staining intensity and distribution patterns. These results were compared with Gleason grade and clinical and pathologic stages. Results.—One hundred thirty-three (63%) of 211 cases showed high expression of CPP32, whereas expression was low in 78 (37%) cases. One hundred three (49%) of 211 cases had a high Gleason score (7 and above). Of 103 cases with a high Gleason score, 74 (72%) showed high CPP32 expression. Strong cytoplasmic staining for CPP32 in high-grade tumors was statistically significant (P = .01). Also, by linear regression analysis a significant correlation was seen between the Gleason score and the cytoplasmic CPP32 expression (P = .001). Expression of CPP32 did not correlate with either clinical stage (P = .28) or pathologic stage (P = .60); however, this study included very few patients with stage IV disease. Conclusion.—The correlation between CPP32 and high tumor grade suggests a CPP32-related high turnover rate in high-grade prostatic adenocarcinoma. Moreover, strong correlation with Gleason grade, a powerful predictor of disease progression and overall survival, suggests potential usefulness of CPP32 as a prognostic factor, especially in limited biopsy samples.

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Tabish, Sana, Erum Khan, Sajid Mushtaq, Usman Hassan y Mudassar Hussain. "Expression of ERG immunohistochemical stain in prostatic adenocarcinoma". PAFMJ 71, n.º 3 (30 de junio de 2021): 985–88. http://dx.doi.org/10.51253/pafmj.v71i3.5518.

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Objective: The objective of my study is to investigate the incidence ERG fusion positive adenocarcinoma and its correlation with gleason grade and gleason group. Methods: it is a descriptive cross sectional study. 100 cases of prostatic adenocarcinoma were retrieved and ERG immunohistochemical stain was applied on all these cases. ERG expression, extent of staining, percentage of tumor cells positive for ERG, pattern of staining were recorded. We found out relationship of ERG expression and gleason grade/ gleason group. Results: ERG expression was seen in 62/100 (62%) cases. mean patient age of ERG positive prostatic adenocarcinoma patients was 69.68years. In GG1 (14.5%) 9 cases exhibited ERG positivity. In GG2-3, 41.93% cases and in GG4-5, 43.54% cases showed ERG expression. Conclusion: To conclude, age of presentation of ERG positive adenocarcinoma was high. ERG expression was seen in 62% of our cases which was much higher than reported in other Asian countries. In our study we found a significant correlation between ERG expression and high gleason grade group.

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Sowalsky, Adam G., Huihui Ye, Glenn J. Bubley y Steven P. Balk. "Clonal Progression of Prostate Cancers from Gleason Grade 3 to Grade 4". Cancer Research 73, n.º 3 (30 de noviembre de 2012): 1050–55. http://dx.doi.org/10.1158/0008-5472.can-12-2799.

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Saika, T., T. Uesugi, K. Edamura, M. Kobuke, H. Nose, S. Ebara, Y. Nasu, N. Katayama, H. Yanai y H. Kumon. "Impact of primary Gleason grade 4 on biochemical recurrence after permanent interstitial brachytherapy in Japanese patients with low- or intermediate-risk prostate cancer." Journal of Clinical Oncology 29, n.º 7_suppl (1 de marzo de 2011): 77. http://dx.doi.org/10.1200/jco.2011.29.7_suppl.77.

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77 Background: To reveal a predictive factor for biochemical recurrence (BCR) after permanent prostate brachytherapy (PPB) using iodine-125 (125I) seed implantation in patients with localized prostate cancer classified as low or intermediate risk based on the National Comprehensive Cancer Network (NCCN) guidelines. Methods: From January 2004 to December 2009, consecutive 418 Japanese patients with clinically localized prostate cancer classified as low or intermediate risk based on the National Comprehensive Cancer Network (NCCN) guidelines were treated by PPB. The clinical factors including pathological data reviewed by central pathologist and follow-up data were prospectively collected. Kaplan-Meier and Cox regression analyses were used to assess the factors associated with BCR. Results: Median follow-up was 36.0 months. The 2, 3, 4 and 5-year BCR free rates using Phoenix definition were 98.3%, 96.0%, 91.6% and 87.0% respectively. On univariate analysis, primary Gleason grade 4 in biopsy specimen was strong predicting factor (p<0.0001), while Gleason sum, age, initial PSA, initial PSA density, T stage and D90 were insignificant factors. Multivariate analysis indicated that primary Gleason grade 4 was most powerful prognostic factor associated with BCR (hazard ratio=10.101, 95% IC 3.080-33.126, p=0.0001). Conclusions: The primary Gleason grade 4 carried a worse BCR than the primary grade 3 in Gleason score 7 prostate cancer. Therefore, the indication for PPB in patients with Gleason sum 4+3 should deserve careful and thoughtful consideration. No significant financial relationships to disclose.

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Yassin, Aksam y Mahmoud Salman. "Is there a protective role of testosterone against high-grade prostate cancer? Incidence and severity of prostate cancer in 553 patients undergoing prostate biopsy in a prospective data register." Journal of Clinical Oncology 35, n.º 6_suppl (20 de febrero de 2017): 128. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.128.

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128 Background: Major concern regarding testosterone therapy (TRT) in middle-aged and elderly men is still prostate safety or cancer Methods: 553 prostate biopsies (2008-2013) were performed at our institute. 22 patients refused biopsy. We investigated incidence and severity of PCa in three groups: hypogonadal (T ≤ 350 ng/dl) men receiving TRT, hypogonadal untreated, and eugonadal men. All groups underwent similar screening intensity of at least once per year. Biopsies were performed when indicated according to EAU guidelines. Results: In 42 hypogonadal men receiving TRT, 7 (16.7%) had a positive biopsy. Of these, 5 had a Gleason score ≤ 6 (71.4%) and 2 subjects a Gleason score > 6 (28.6%). Predominant Gleason score was 3 in all 7 men (100%). Tumor grade was II in 6 (85.7%) and II-III in 1 (14.3%) men. 162 untreated hypogonadal men, 84 (51.9%) had a positive biopsy. Of these, 34 had a Gleason score ≤ 6 (40.5%) and 50 a Gleason score > 6 (59.5%). Predominant Gleason score was 3 in 65 (77.4%), 4 in 17 (20.2%) and 5 in 2 (2.4%) men. Tumor grade was II in 35 (41.7%), II-III in 10 (11.9%), III in 34 (40.5%) and IV in 5 (6.0%) men. In 349 eugonadal men, 132 (37.8%) had a positive biopsy. Of these, 56 had a Gleason score ≤ 6 (42.4%) and 76 a Gleason score > 6 (57.6%). Predominant Gleason score was 3 in 109 (82.6%), 4 in 22 (16.7%) and 5 in 1 (0.1%) men. Tumor grade was II in 59 (44.7%), II-III in 6 (4.5%), III in 63 (47.7%) and IV in 4 (3.0%) men. Conclusions: The incidence of positive prostate biopsies was lowest in hypogonadal men receiving TRT. The severity of PCa – in terms of Staging and Grading - was significantly lower in hypogonadal patients receiving TRT. TRT may protect against high-grade PCa. Protective role of TRT against PCa must be discussed and considered in larger studies.

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Mahal, Brandon Arvin Virgil, David Dewei Yang, Natalie Wang, Mohammed Alshalalfa, Elai Davicioni, Voleak Choeurng, Daniel Eidelberg Spratt et al. "Clinical and genomic characterization of low-prostate-specific antigen, high-grade prostate cancer." Journal of Clinical Oncology 36, n.º 6_suppl (20 de febrero de 2018): 59. http://dx.doi.org/10.1200/jco.2018.36.6_suppl.59.

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59 Background: The consequences of a low prostate-specific antigen (PSA) in high-grade (Gleason 8-10) prostate cancer are unknown. We sought to evaluate the clinical implications and genomic features of this entity. Methods: Clinical and transcriptomic data from 626,057 patients with N0M0 prostate cancer were collected from two national cohorts and a large transcriptome database. Multivariable Fine-Gray and Cox regressions analyzed prostate-cancer specific mortality (PCSM) and all-cause mortality, respectively. GRID data were used to analyze transcriptomic features. Results: For Gleason 8-10 disease, the distribution of PCSM was U-shaped by PSA (PSA 4.1-10.0 ng/mL = referent), with adjusted hazard ratio (AHR) 2.70 for PSA ≤2.5 ng/mL (P < 0.001) versus 1.97, 1.36, and 2.56 for PSA 2.6-4.0, 10.1-20.0, and > 20.0 ng/mL, respectively. In contrast, distribution of PCSM by PSA was linear for Gleason ≤7 with AHR 0.41 for PSA ≤2.5 ng/mL (P = 0.127) versus 1.38, 2.28, and 4.61 for PSA 2.6-4.0, 10.1-20.0, and > 20.0 ng/mL, respectively (PGleason*PSA interaction< 0.001). Gleason 8-10, PSA ≤2.5 ng/mL disease had a significantly higher PCSM than standard high and very high-risk disease with PSA > 2.5 ng/mL (AHR 2.15, P = 0.009; 47-month PCSM 13.8% versus 4.9%). Among Gleason 8-10 patients treated with definitive radiotherapy, androgen deprivation therapy (ADT) was associated with a survival benefit for PSA > 2.5 ng/mL (AHR 0.87, P < 0.001) but not for ≤2.5ng/mL (AHR 1.36, P = 0.084; PADT*PSA interaction= 0.021). For Gleason 8-10 tumors, PSA ≤2.5 ng/mL was associated with a higher expression of neuroendocrine markers compared to > 2.5 ng/mL (P = 0.046), with no such relationship for Gleason ≤7. Conclusions: Low-PSA, high-grade prostate cancer appears to be a unique entity that has a very high risk for PCSM, potentially responds poorly to ADT, and is associated with neuroendocrine genomic features.

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van Leeuwen, Pim J., Amila Siriwardana, Monique Roobol, Francis Ting, Daan Nieboer, James Thompson, Warick Delprado, Anne-Marie Haynes, Phillip Brenner y Phillip Stricker. "Predicting Low-Risk Prostate Cancer from Transperineal Saturation Biopsies". Prostate Cancer 2016 (2016): 1–7. http://dx.doi.org/10.1155/2016/7105678.

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Introduction. To assess the performance of five previously described clinicopathological definitions of low-risk prostate cancer (PC).Materials and Methods. Men who underwent radical prostatectomy (RP) for clinical stage ≤T2, PSA <10 ng/mL, Gleason score <8 PC, diagnosed by transperineal template-guided saturation biopsy were included. The performance of five previously described criteria (i.e., criteria 1–5, criterion 1 stringent (Gleason score 6 + ≤5 mm total max core length PC + ≤3 mm max per core length PC) up to criterion 5 less stringent (Gleason score 6-7 with ≤5% Gleason grade 4) was analysed to assess ability of each to predict insignificant disease in RP specimens (defined as Gleason score ≤6 and total tumour volume <2.5 mL, or Gleason score 7 with ≤5% grade 4 and total tumour volume <0.7 mL).Results. 994 men who underwent RP were included. Criterion 4 (Gleason score 6) performed best with area under the curve of receiver operating characteristics 0.792. At decision curve analysis, criterion 4 was deemed clinically the best performing transperineal saturation biopsy-based definition for low-risk PC.Conclusions. Gleason score 6 disease demonstrated a superior trade-off between sensitivity and specificity for clarifying low-risk PC that can guide treatment and be used as reference test in diagnostic studies.

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Poulos, Chistopher K., Joanne K. Daggy y Liang Cheng. "Preoperative prediction of Gleason grade in radical prostatectomy specimens: the influence of different Gleason grades from multiple positive biopsy sites". Modern Pathology 18, n.º 2 (8 de octubre de 2004): 228–34. http://dx.doi.org/10.1038/modpathol.3800302.

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Ritenour, Chad W. M., John T. Abbott, Michael Goodman, Naomi Alazraki, Fray F. Marshall y Muta M. Issa. "The Utilization of Gleason Grade as the Primary Criterion for Ordering Nuclear Bone Scan in Newly Diagnosed Prostate Cancer Patients". Scientific World JOURNAL 9 (2009): 1040–45. http://dx.doi.org/10.1100/tsw.2009.113.

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Utilization of nuclear bone scans for staging newly diagnosed prostate cancer has decreased dramatically due to PSA-driven stage migration. The current criteria for performing bone scans are based on limited historical data. This study evaluates serum PSA and Gleason grade in predicting positive scans in a contemporary large series of newly diagnosed prostate cancer patients. Eight hundred consecutive cases of newly diagnosed prostate cancer over a 64-month period underwent a staging nuclear scan. All subjects had histologically confirmed cancer. The relationship between PSA, Gleason grade, and bone scan was examined by calculating series of crude, stratified, and adjusted odds ratios with corresponding 95% confidence intervals. Four percent (32/800) of all bone scans were positive. This proportion was significantly lower in patients with Gleason score ≤7 (1.9%) vs. Gleason score ≥8 (18.8%,p< 0.001). Among patients with Gleason score ≤7, the rate of positive bones scans was 70-fold higher when the PSA was >30 ng/ml compared to ≤30 ng/ml (p< 0.001). For Gleason score ≥8, the rate was significantly higher (27.9 vs. 0%) when PSA was >10 ng/ml compared to ≤10 ng/ml (p= 0.002). The combination of Gleason score and PSA enhances predictability of bone scans in newly diagnosed prostate cancer patients. The PSA threshold for ordering bone scans should be adjusted according to Gleason score. For patients with Gleason scores ≤7, we recommend a bone scan if the PSA is >30 ng/ml. However, for patients with a high Gleason score (8–10), we recommend a bone scan if the PSA is >10 ng/ml.

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Qian, Hongyang, Xiaoguang Shao, Yinjie Zhu, Liancheng Fan, Heng Zhang, Baijun Dong, Yanqing Wang et al. "Surface-enhanced Raman spectroscopy of preoperative serum samples predicts Gleason grade group upgrade in biopsy Gleason grade group 1 prostate cancer". Urologic Oncology: Seminars and Original Investigations 38, n.º 6 (junio de 2020): 601.e1–601.e9. http://dx.doi.org/10.1016/j.urolonc.2020.02.009.

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Merriel, Samuel William David, Emma L. Turner, Eleanor Walsh, Grace J. Young, Chris Metcalfe, Luke Hounsome, Isobel Tudge et al. "Cross-sectional study evaluating data quality of the National Cancer Registration and Analysis Service (NCRAS) prostate cancer registry data using the Cluster randomised trial of PSA testing for Prostate cancer (CAP)". BMJ Open 7, n.º 11 (noviembre de 2017): e015994. http://dx.doi.org/10.1136/bmjopen-2017-015994.

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ObjectivesTo compare the completeness and agreement of prostate cancer data recorded by the National Cancer Registration and Analysis Service (NCRAS) with research-level data specifically abstracted from medical records from the Cluster randomised triAl of prostate specific antigen (PSA) testing for Prostate cancer (CAP) trial.DesignCross-sectional comparison study.ParticipantsWe included 1356 men from the CAP trial cohort who were linked to the NCRAS registry.Primary and secondary outcome measuresCompleteness of prostate cancer data in NCRAS and CAP and agreement for tumour, node, metastases (TNM) stage (T1/T2; T3; T4/N1/M1) and Gleason grade (4–6; 7; 8–10), measured by differences in proportions and Cohen’s kappa statistic. Data were also stratified by year and pre-2010 versus post-2010, when NCRAS reporting standards changed.ResultsCompared with CAP, completeness was lower in NCRAS for Gleason grade (41.2% vs 76.7%, difference 35.5, 95% CI 32.1 to 39.0) and TNM stage (29.9% vs 67.6%, difference 37.6, 95% CI 34.1 to 41.1). NCRAS completeness for Gleason grade (pre-2010 vs post-2010 31.69% vs 64%; difference 32.31, 95% CI 26.76 to 37.87) and TNM stage (19.31% vs 55.50%; difference 36.19, 95% CI 30.72 to 41.67) improved over time. Agreement for Gleason grade was high (Cohen’s kappa, κ=0.90, 95% CI 0.88 to 0.93), but lower for TNM stage (κ=0.41, 95% CI 0.37 to 0.51) overall. There was a trend towards improved agreement on Gleason grade, but not TNM stage, when comparing pre-2010 and post-2010 data.ConclusionNCRAS case identification was very high; however, data on prostate cancer grade was less complete than CAP, and agreement for TNM stage was modest. Although the completeness of NCRAS data has improved since 2010, the higher completeness rate in CAP demonstrates that gains could potentially be achieved in routine registry data. This study’s findings highlight a need for improved recording of stage and grade data in the source medical records.

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Boag, A. H., L. A. Kennedy y M. J. Miller. "Three-Dimensional Microscopic Image Reconstruction of Prostatic Adenocarcinoma". Archives of Pathology & Laboratory Medicine 125, n.º 4 (1 de abril de 2001): 562–66. http://dx.doi.org/10.5858/2001-125-0562-tdmiro.

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Abstract Context.—Routine microscopy provides only a 2-dimensional view of the complex 3-dimensional structure that makes up human tissue. Three-dimensional microscopic image reconstruction has not been described previously for prostate cancer. Objectives.—To develop a simple method of computerized 3-dimensional image reconstruction and to demonstrate its applicability to the study of prostatic adenocarcinoma. Methods.—Serial sections were cut from archival paraffin-embedded prostate specimens, immunostained using antikeratin CAM5.2, and digitally imaged. Computer image–rendering software was used to produce 3-dimensional image reconstructions of prostate cancer of varying Gleason grades, normal prostate, and prostatic intraepithelial neoplasia. Results.—The rendering system proved easy to use and provided good-quality 3-dimensional images of most specimens. Normal prostate glands formed irregular fusiform structures branching off central tubular ducts. Prostatic intraepithelial neoplasia showed external contours similar to those of normal glands, but with a markedly complex internal arrangement of branching lumens. Gleason grade 3 carcinoma was found to consist of a complex array of interconnecting tubules rather than the apparently separate glands seen in 2 dimensions on routine light microscopy. Gleason grade 4 carcinoma demonstrated a characteristic form of glandular fusion that was readily visualized by optically sectioning and rotating the reconstructed images. Conclusions.—Computerized 3-dimensional microscopic imaging holds great promise as an investigational tool. By revealing the structural relationships of the various Gleason grades of prostate cancer, this method could be used to refine diagnostic and grading criteria for this common tumor.

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Shah, Manan B., Kalyani Raju y Harish Kumar G. "Revisiting Prostate Biopsy with 2014 ISUP Modified Gleason Score and Gleason Grade – A Cross Section Study". Biomedical Research and Therapy 5, n.º 12 (27 de diciembre de 2018): 2918–25. http://dx.doi.org/10.15419/bmrat.v5i12.511.

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Background: Prostatic carcinoma is one of the most common carcinomas among men throughout the world. Gleason score (GS) system is used in reporting and assessing the prognosis of prostatic carcinoma. The GS has undergone modifications. The objective of this study is to evaluate the impact of the new 2014 ISUP Modified Gleason System and Gleason grading (GG) on reporting of prostatic carcinoma. Methodology: This is a retrospective Study. All cases reported as adenocarcinoma prostate from January 2013 to July 2018 were included in the study. The GS done previously as per 2005 criteria was noted. The GS system and GG were done on the microslides retrieved as per 2015 criteria and compared with that of GS already recorded and also with old risk stratification. Results: Comparing the GS of 2005 and 2015 criteria, there was a marked decrease (80%) in Gleason score 6; among these cases, 80% cases were graded as score 7, and 20% cases were graded as score 8. There is also a 28.57% decrease in Gleason score 8 and 60% increase in Gleason score 9 due to the new criteria for pattern 4. The GG 1,2,3,4 and 5 constituted 3.03%, 18.18%, 15.15%, 15.15%, and 48.49% of cases respectively. Conclusion: The new GS and GG has more impact on prognosis of adenocarcinoma prostate as GS 6 has better prognosis and GG gives better risk stratification compared to the previous risk stratification.

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Montironi, Rodolfo, Matteo Santoni, Roberta Mazzucchelli, Luciano Burattini, Rossana Berardi, Andrea B. Galosi, Liang Cheng et al. "Prostate cancer: from Gleason scoring to prognostic grade grouping". Expert Review of Anticancer Therapy 16, n.º 4 (23 de marzo de 2016): 433–40. http://dx.doi.org/10.1586/14737140.2016.1160780.

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Egevad, Lars, Hemamali Samaratunga, John R. Srigley y Brett Delahunt. "Re: Consensus Guidelines for Reporting Prostate Cancer Gleason Grade". Journal of Urology 196, n.º 4 (octubre de 2016): 1321–23. http://dx.doi.org/10.1016/j.juro.2016.07.069.

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Atallah, Chantal, Ants Toi y Theodorus H. van der Kwast. "Gleason grade 5 prostate cancer: sub-patterns and prognosis". Pathology 53, n.º 1 (enero de 2021): 3–11. http://dx.doi.org/10.1016/j.pathol.2020.09.016.

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Delahunt, Brett, Lars Egevad, Hemamali Samaratunga, Guido Martignoni, John N. Nacey y John R. Srigley. "Reply: Gleason and Fuhrman no longer make the grade". Histopathology 69, n.º 2 (5 de abril de 2016): 341–42. http://dx.doi.org/10.1111/his.12947.

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Kishan, Amar U., Tahmineh Romero, Mohammed Alshalalfa, Yang Liu, Phuoc T. Tran, Nicholas G. Nickols, Huihui Ye et al. "Transcriptomic Heterogeneity of Gleason Grade Group 5 Prostate Cancer". European Urology 78, n.º 3 (septiembre de 2020): 327–32. http://dx.doi.org/10.1016/j.eururo.2020.05.009.

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Hatano, Koji, Junichiro Tanaka, Yasutomo Nakai, Masashi Nakayama, Ken-ichi Kakimoto, Katsuyuki Nakanishi y Kazuo Nishimura. "Utility of index lesion volume assessed by multiparametric MRI combined with Gleason grade for assessment of lymph node involvement in patients with high-risk prostate cancer". Japanese Journal of Clinical Oncology 50, n.º 3 (12 de diciembre de 2019): 333–37. http://dx.doi.org/10.1093/jjco/hyz170.

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Abstract Purpose We examined the potential predictors of lymph node involvement and evaluated whether index lesion volume assessed using multiparametric magnetic resonance imaging is associated with lymph node involvement among patients with high-risk prostate cancer. Methods Extended pelvic lymph node dissection was used to evaluate patients with lymph node involvement. We retrospectively analyzed consecutive 102 patients with high-risk prostate cancer who underwent extended pelvic lymph node dissection at our institution between 2011 and 2017. To evaluate the index lesion volume at multiparametric magnetic resonance imaging (mrV), lesions were manually contoured on each T2-weighted axial slice in combination with diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging and integrated using image analysis software. Logistic regression analysis was performed to identify predictors of lymph node involvement. Results The median mrV was 1.4 ml (range 0–30.1 ml), and the median number of resected lymph nodes was 14 (range 7–38). Among 102 patients, 28 (28%) had lymph node involvement. Multivariate analysis identified significant predictors of lymph node involvement as follows: biopsy Gleason-grade group 5 (odds ratio = 17.2; 95% confidence interval, 2.1–299.0; P = 0.005), preoperative mrV (odds ratio = 1.14; 95% confidence interval, 1.02–1.30; P = 0.025) and percentage of positive cores with highest Gleason-grade group (odds ratio = 1.05; 95% confidence interval, 1.01–1.10; P = 0.005). Lymph node involvement was prevalent (69%) among tumors with Gleason-grade group 5 and mrV ≥3.4 ml, but was infrequently (10%) present among tumors with Gleason-grade group ≤4 and mrV <3.4 ml. Conclusions The combination of biopsy Gleason-grade and mrV may serve as a useful tool to stratify patients according to their risk of nodal metastases.

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