Journal articles: 'Melan-A'

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Pittet, Mikaël J., Danila Valmori, P. Rod Dunbar, Daniel E. Speiser, Danielle Liénard, Ferdy Lejeune, Katharina Fleischhauer, Vincenzo Cerundolo, Jean-Charles Cerottini, and Pedro Romero. "High Frequencies of Naive Melan-a/Mart-1–Specific Cd8+ T Cells in a Large Proportion of Human Histocompatibility Leukocyte Antigen (Hla)-A2 Individuals." Journal of Experimental Medicine 190, no. 5 (September 6, 1999): 705–16. http://dx.doi.org/10.1084/jem.190.5.705.

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Using fluorescent HLA-A*0201 tetramers containing the immunodominant Melan-A/MART-1 (Melan-A) tumor-associated antigen (Ag), we previously observed that metastatic lymph nodes of melanoma patients contain high numbers of Ag-experienced Melan-A–specific cytolytic T lymphocytes (CTLs). In this paper, we enumerated and characterized ex vivo Melan-A–specific cells in peripheral blood samples from both melanoma patients and healthy individuals. High frequencies (≥1 in 2,500 CD8+ T cells) of Melan-A–specific cells were found in 10 out of 13 patients, and, surprisingly, in 6 out of 10 healthy individuals. Virtually all Melan-A–specific cells from 6 out of 6 healthy individuals and from 7 out of 10 patients displayed a naive CD45RAhi/RO− phenotype, whereas variable proportions of Ag-experienced CD45RAlo/RO+ Melan-A–specific cells were observed in the remaining 3 patients. In contrast, ex vivo influenza matrix–specific CTLs from all individuals exhibited a CD45RAlo/RO+ memory phenotype as expected. Ag specificity of tetramer-sorted A2/Melan-A+ cells from healthy individuals was confirmed after mitogen-driven expansion. Likewise, functional limiting dilution analysis and interferon γ ELISPOT assays independently confirmed that most of the Melan-A–specific cells were not Ag experienced. Thus, it appears that high frequencies of naive Melan-A–specific CD8+ T cells can be found in a large proportion of HLA-A*0201+ individuals. Furthermore, as demonstrated for one patient followed over time, dramatic phenotype changes of circulating Melan-A–specific cells can occur in vivo.

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Tuna, Emine Burçin, Banu Lebe, and Kutsal Yörükoğlu. "HMB45 and Melan-A Expression in Renal Angiomyolipoma and Their Significance for the Diagnosis." Tumori Journal 89, no. 1 (January 2003): 46–48. http://dx.doi.org/10.1177/030089160308900110.

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Aims and Background The melanosome-associated proteins, also called HMB45 and melan-A, are also present in renal angiomyolipoma. The aim of the present study was to evaluate the expression of HMB45 and melan-A in mesenchymal cells of renal angiomyolipoma and to investigate their significance in the differential diagnosis. Methods Twelve patients, 9 females and 3 males diagnosed with renal angiomyolipomas, were included in the present study. The most representative tumor tissue block was chosen from each case, and 5-üm sections were taken to poly-l-lysin-coated slides for immunohistochemical staining. The standard streptavidin-biotin immunoperoxidase method was used for immunostaining with HMB45 and melan-A antibodies. Results All of the cases showed positive cytoplasmic immunostaining for HMB45 and melan-A. Melan-A expression was shown in smooth muscle component, adipose tissue and predominantly in the perivascular cells, whereas HMB45 immunoreactivity was stronger than melan-A expression in all cases. Conclusions It was concluded that HMB45 and melan-A reactivity is a useful tool to distinguish renal angiomyolipomas from other primary and secondary mesenchymal and primary epithelial tumors. Melan-A and HMB45 share similar specificities for renal angiomyolipoma. In addition, such expression in renal angiomyolipomas may occur without any evidence of nevomelanocytic differentiation. Further research is required to determine the histogenesis of this entity.

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Spanakis, E., P. Lamina, and D. C. Bennett. "Effects of the developmental colour mutations silver and recessive spotting on proliferation of diploid and immortal mouse melanocytes in culture." Development 114, no. 3 (March 1, 1992): 675–80. http://dx.doi.org/10.1242/dev.114.3.675.

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The developmental mouse coat-colour mutations silver (si, chromosome 10) and recessive spotting (rs, chromosome 5, mapping very close to the dominant white spotting or W/c-kit locus), appear to reduce the numbers of functional melanocytes in the skin. They were studied at the cellular level by melanocyte culture. Cellular morphology, differentiation and survival appeared normal. However, both mutations were found to reduce the melanocyte proliferation rate in primary cultures, as measured by [3H]thymidine labelling indices. Two immortal si/si melanocyte lines (designated melan-si1 and melan-si2) and one rs/rs line (melan-rs) were established. Melan-si1 and melan-rs were cloned. All three immortal lines at low passage levels had doubling times significantly greater than those of our other melanocyte lines melan-a, melan-b and melan-c. Thus they retained the phenotype of slow proliferation.

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Vaniary, Tjokorde Istri Nindya, M. Yulianto Listiawan, and Dwi Murtiastutik. "Expression of Melan-A in Depigmented Skin of Vitiligo Patients." Berkala Ilmu Kesehatan Kulit dan Kelamin 32, no. 1 (March 31, 2020): 17. http://dx.doi.org/10.20473/bikk.v32.1.2020.17-20.

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Background: Vitiligo is an acquired and commonly found pigmentation disorder characterized by milky-white patches on the skin, hair, and mucosa due to melanocyte damage. The cause of vitiligo is still unclear. A study proves that cell-mediated immunity plays a role in the pathogenesis of vitiligo. Melan-A is a melanoma-related antigen that is recognized by autologous cytotoxic T cells and one of the critical markers for detecting melanocytes. Objective: To evaluate the expression of Melan-A in depigmented lesions of vitiligo patients. Methods: A descriptive study aimed to describe the expression of Melan-A in the depigmented skin of vitiligo patients at the Dermatovenerology Outpatient Clinic Cosmetic Division of Academic General Hospital Dr. Soetomo Surabaya. Eleven study subjects were selected through a sequence of selection. Results: Melan-A expression in the depigmented skin of vitiligo patients was lower than the average. This result was found in 6 (54.55%) out of 11 patients. Conclusion: Melan-A expressions on depigmented skins of vitiligo patients are generally below the average value; therefore, adequate intervention is needed to increase the Melan-A expression.

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Guler, Mehmet L., Jason A. Daniels, Susan C. Abraham, and Elizabeth A. Montgomery. "Expression of Melanoma Antigens in Epithelioid Gastrointestinal Stromal Tumors: A Potential Diagnostic Pitfall." Archives of Pathology & Laboratory Medicine 132, no. 8 (August 1, 2008): 1302–6. http://dx.doi.org/10.5858/2008-132-1302-eomaie.

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Abstract Context.—Most gastric gastrointestinal stromal tumors (GISTs) express CD117/c-kit, as do a subset of metastatic melanomas, leading to a diagnostic dilemma in some cases. Objective.—To further differentiate GISTs from melanoma, we investigated expression of melanoma markers in GISTs using a well-characterized set of gastric lesions on tissue microarrays. Design.—Tissue microarrays from paraffin-embedded tissue cores from 38 patients were stained with S100 protein, HMB-45, and Melan-A antibodies. All cases had been previously stained with CD117/c-kit and CD34 antibodies. All were reactive with CD117/c-kit, and 88.2% expressed CD34. Results.—S100 protein was focally expressed in 2 (5.3%) of 38 GISTs; these lesions lacked HMB-45 and Melan-A labeling. No tumor labeled with HMB-45, but 4 (10.6%) of 38 cases labeled with Melan-A antibodies. The Melan-A–reactive cases were all S100 negative and CD34 positive. The S100-reactive cases were spindle cell neoplasms, whereas the Melan-A–reactive cases were epithelioid neoplasms (4/9; 44%). An additional 15 standard sections of separate cases of epithelioid GISTs were then labeled with Melan-A, and 5 (33%) of 15 showed at least focal labeling. Conclusions.—Melan-A staining can be encountered in a subset of epithelioid GISTs, a finding that can suggest a differential diagnosis of melanoma. In this series, the Melan-A–reactive cases lacked S100 protein and expressed CD34, both of which would be unlikely in melanoma. As such, a panel approach is best in differentiating epithelioid GISTs from melanoma.

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Lévy, Frédéric, Katja Muehlethaler, Suzanne Salvi, Anne-Lise Peitrequin, Cecilia K. Lindholm, Jean-Charles Cerottini, and Donata Rimoldi. "Ubiquitylation of a Melanosomal Protein by HECT-E3 Ligases Serves as Sorting Signal for Lysosomal Degradation." Molecular Biology of the Cell 16, no. 4 (April 2005): 1777–87. http://dx.doi.org/10.1091/mbc.e04-09-0803.

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The production of pigment by melanocytic cells of the skin involves a series of enzymatic reactions that take place in specialized organelles called melanosomes. Melan-A/MART-1 is a melanocytic transmembrane protein with no enzymatic activity that accumulates in vesicles at the trans side of the Golgi and in melanosomes. We show here that, in melanoma cells, Melan-A associates with two homologous to E6-AP C-terminus (HECT)-E3 ubiquitin ligases, NEDD4 and Itch, and is ubiquitylated. Both NEDD4 and Itch participate in the degradation of Melan-A. A mutant Melan-A lacking ubiquitin-acceptor residues displays increased half-life and, in pigmented cells, accumulates in melanosomes. These results suggest that ubiquitylation regulates the lysosomal sorting and degradation of Melan-A/MART-1 from melanosomes in melanocytic cells.

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Weide, Benjamin, Henning Zelba, Evelyna Derhovanessian, Annette Pflugfelder, Thomas K. Eigentler, Anna Maria Di Giacomo, Michele Maio, et al. "Functional T Cells Targeting NY-ESO-1 or Melan-A Are Predictive for Survival of Patients With Distant Melanoma Metastasis." Journal of Clinical Oncology 30, no. 15 (May 20, 2012): 1835–41. http://dx.doi.org/10.1200/jco.2011.40.2271.

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Purpose To analyze the prognostic relevance of circulating T cells responding to NY-ESO-1, Melan-A, MAGE-3, and survivin in patients with melanoma with distant metastasis. Patients and Methods We examined 84 patients with follow-up after analysis (cohort A), 18 long-term survivors with an extraordinarily favorable course of disease before analysis (> 24 months survival after first occurrence of distant metastases; cohort B), and 14 healthy controls. Circulating antigen-reactive T cells were characterized by intracellular cytokine staining after in vitro stimulation. Results In cohort A patients, the presence of T cells responding to peptides from NY-ESO-1, Melan-A, or MAGE-3 and the M category according to the American Joint Committee on Cancer classification were significantly associated with survival. T cells responding to NY-ESO-1 and Melan-A (hazard ratios, 0.29 and 0.18, respectively) remained independent prognostic factors in Cox regression analysis and were superior to the M category in predicting outcome. Median survival of patients possessing T cells responding to NY-ESO-1, Melan-A, or both was 21 months, compared with 6 months for all others. NY-ESO-1–responsive T cells were detected in 70% of cohort A patients surviving > 18 months and in 50% of cohort B patients. Melan-A responses were found in 42% and 47% of patients in cohorts A and B, respectively. In contrast, the proportion was only 22% for NY-ESO-1 and 23% for Melan-A in those who died within 6 months. Conclusion The presence of circulating T cells responding to Melan-A or NY-ESO-1 had strong independent prognostic impact on survival in advanced melanoma. Our findings support the therapeutic relevance of Melan-A and NY-ESO-1 as targets for immunotherapy.

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Chen, Yumei, Paul W. Klonowski, Anne C. Lind, and Dongsi Lu. "Differentiating Neurotized Melanocytic Nevi From Neurofibromas Using Melan-A (MART-1) Immunohistochemical Stain." Archives of Pathology & Laboratory Medicine 136, no. 7 (July 1, 2012): 810–15. http://dx.doi.org/10.5858/arpa.2011-0335-oa.

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Context.—Neurotized melanocytic nevi and neurofibromas are common, benign cutaneous neoplasms. Usually they are histologically distinct from each other; however, neurotized melanocytic nevi and neurofibromas can be clinically and histologically similar. Objective.—To determine whether Melan-A (MART-1) immunohistochemical stain is sufficient to differentiate neurotized melanocytic nevi from neurofibromas. Design.—Forty-nine consecutive specimens of melanocytic nevi with neurotization and 49 specimens of neurofibromas were selected. We used antibodies against Melan-A, S100, and neurofilament protein. Results.—All of the melanocytic nevi showed Melan-A staining within the neurotized areas, with most of the areas staining strongly positive, whereas all the neurofibromas were completely absent of Melan-A stain. All of the nevi, including the neurotized areas, stained strongly and diffusely for S100, whereas all the neurofibromas showed a distinctive, sharp, wavy pattern of S100 staining. Neurofilament protein showed scattered staining of both melanocytic nevi and neurofibromas. Conclusions.—Our data indicate that Melan-A immunohistochemical staining is helpful in differentiating neurotized melanocytic nevi from neurofibromas when distinction on histomorphology alone is difficult.

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Andres, Christian, and Michael J. Flaig. "Pitfalls of Melan-A staining." Journal of Cutaneous Pathology 37, no. 8 (October 5, 2009): 917–18. http://dx.doi.org/10.1111/j.1600-0560.2009.01442.x.

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Chen, Kun, Prashiela Manga, and Seth J. Orlow. "Pink-eyed Dilution Protein Controls the Processing of Tyrosinase." Molecular Biology of the Cell 13, no. 6 (June 2002): 1953–64. http://dx.doi.org/10.1091/mbc.02-02-0022.

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The processing of tyrosinase, which catalyzes the limiting reaction in melanin synthesis, was investigated in melan-p1 melanocytes, which are null at the p locus. Endoglycosidase H digestion showed that a significant fraction of tyrosinase was retained in the endoplasmic reticulum. This retention could be rescued either by transfection of melan-p1 cells with an epitope-tagged wild-typep transcript or by treatment with either bafilomycin A1 or ammonium chloride. We found that the endoplasmic reticulum contains a significant amount of p protein, thus supporting a role for p within this compartment. Using immunofluoresence, we showed that most mature full-length tyrosinase in melan-p1 cells was located in the perinuclear area near the Golgi, in contrast to its punctate melanosomal pattern in wild-type melanocytes. Expression of p in melan-p1 cells restored tyrosinase to melanosomes. Triton X-114 phase separation revealed that an increased amount of tyrosinase was proteolyzed in melan-p1 cells compared with wild-type melanocytes. The proteolyzed tyrosinase was no longer membrane bound, but remained enzymatically active and a large proportion was secreted into the culture medium of melan-p1 cells. We conclude that p regulates posttranslational processing of tyrosinase, and hypopigmentation in melan-p1 cells is the result of altered tyrosinase processing and trafficking.

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Viray, Hollis, William R. Bradley, Kurt A. Schalper, David L. Rimm, and Bonnie E. Gould Rothberg. "Marginal and Joint Distributions of S100, HMB-45, and Melan-A Across a Large Series of Cutaneous Melanomas." Archives of Pathology & Laboratory Medicine 137, no. 8 (August 1, 2013): 1063–73. http://dx.doi.org/10.5858/arpa.2012-0284-oa.

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Context.—The distribution of the standard melanoma antibodies S100, HMB-45, and Melan-A has been extensively studied. Yet, the overlap in their expression is less well characterized. Objectives.—To determine the joint distributions of the classic melanoma markers and to determine if classification according to joint antigen expression has prognostic relevance. Design.—S100, HMB-45, and Melan-A were assayed by immunofluorescence-based immunohistochemistry on a large tissue microarray of 212 cutaneous melanoma primary tumors and 341 metastases. Positive expression for each antigen required display of immunoreactivity for at least 25% of melanoma cells. Marginal and joint distributions were determined across all markers. Bivariate associations with established clinicopathologic covariates and melanoma-specific survival analyses were conducted. Results.—Of 322 assayable melanomas, 295 (91.6%), 203 (63.0%), and 236 (73.3%) stained with S100, HMB-45, and Melan-A, respectively. Twenty-seven melanomas, representing a diverse set of histopathologic profiles, were S100 negative. Coexpression of all 3 antibodies was observed in 160 melanomas (49.7%). Intensity of endogenous melanin pigment did not confound immunolabeling. Among primary tumors, associations with clinicopathologic parameters revealed a significant relationship only between HMB-45 and microsatellitosis (P = .02). No significant differences among clinicopathologic criteria were observed across the HMB-45/Melan-A joint distribution categories. Neither marginal HMB-45 (P = .56) nor Melan-A (P = .81), or their joint distributions (P = .88), was associated with melanoma-specific survival. Conclusions.—Comprehensive characterization of the marginal and joint distributions for S100, HMB-45, and Melan-A across a large series of cutaneous melanomas revealed diversity of expression across this group of antigens. However, these immunohistochemically defined subclasses of melanomas do not significantly differ according to clinicopathologic correlates or outcome.

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Chen, Q., H. Jackson, J. Cebon, P. Gibbs, I. D. Davis, and J. A. Trapani. "A direct comparison of cytolytic T-lymphocyte responses to Melan-A peptides in vitro: differential immunogenicity of Melan-A27-35 and Melan-A26-35." Melanoma Research 10, no. 1 (February 2000): 16–25. http://dx.doi.org/10.1097/00008390-200002000-00003.

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Chen, Q., H. Jackson, J. Cebon, P. Gibbs, I. D. Davis, and J. A. Trapani. "A direct comparison of cytolytic T-lymphocyte responses to Melan-A peptides in vitro: differential immunogenicity of Melan-A27-35 and Melan-A26-35." Melanoma Research 10, no. 1 (February 2000): 16–25. http://dx.doi.org/10.1097/00008390-200010010-00003.

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Dutoit, Valérie, Verena Rubio-Godoy, Mikäel J. Pittet, Alfred Zippelius, Pierre-Yves Dietrich, Frédérique Anne Legal, Philippe Guillaume, et al. "Degeneracy of Antigen Recognition as the Molecular Basis for the High Frequency of Naive A2/Melan-A Peptide Multimer+ CD8+ T Cells in Humans." Journal of Experimental Medicine 196, no. 2 (July 15, 2002): 207–16. http://dx.doi.org/10.1084/jem.20020242.

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In contrast with the low frequency of most single epitope reactive T cells in the preimmune repertoire, up to 1 of 1,000 naive CD8+ T cells from A2+ individuals specifically bind fluorescent A2/peptide multimers incorporating the A27L analogue of the immunodominant 26–35 peptide from the melanocyte differentiation and melanoma associated antigen Melan-A. This represents the only naive antigen-specific T cell repertoire accessible to direct analysis in humans up to date. To get insight into the molecular basis for the selection and maintenance of such an abundant repertoire, we analyzed the functional diversity of T cells composing this repertoire ex vivo at the clonal level. Surprisingly, we found a significant proportion of multimer+ clonotypes that failed to recognize both Melan-A analogue and parental peptides in a functional assay but efficiently recognized peptides from proteins of self- or pathogen origin selected for their potential functional cross-reactivity with Melan-A. Consistent with these data, multimers incorporating some of the most frequently recognized peptides specifically stained a proportion of naive CD8+ T cells similar to that observed with Melan-A multimers. Altogether these results indicate that the high frequency of Melan-A multimer+ T cells can be explained by the existence of largely cross-reactive subsets of naive CD8+ T cells displaying multiple specificities.

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Zippelius, Alfred, Mikaël J. Pittet, Pascal Batard, Nathalie Rufer, Magda de Smedt, Philippe Guillaume, Kim Ellefsen, et al. "Thymic Selection Generates a Large T Cell Pool Recognizing a Self-Peptide in Humans." Journal of Experimental Medicine 195, no. 4 (February 18, 2002): 485–94. http://dx.doi.org/10.1084/jem.20011658.

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The low frequency of self-peptide–specific T cells in the human preimmune repertoire has so far precluded their direct evaluation. Here, we report an unexpected high frequency of T cells specific for the self-antigen Melan-A/MART-1 in CD8 single–positive thymocytes from human histocompatibility leukocyte antigen-A2 healthy individuals, which is maintained in the peripheral blood of newborns and adults. Postthymic replicative history of Melan-A/MART-1–specific CD8 T cells was independently assessed by quantifying T cell receptor excision circles and telomere length ex vivo. We provide direct evidence that the large T cell pool specific for the self-antigen Melan-A/MART-1 is mostly generated by thymic output of a high number of precursors. This represents the only known naive self-peptide–specific T cell repertoire directly accessible in humans.

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Busam, K. J., and A. A. Jungbluth. "Melan-A, A New Melanocytic Differentiation Marker." Advances in Anatomic Pathology 6, no. 1 (January 1999): 12–18. http://dx.doi.org/10.1097/00125480-199901000-00002.

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Ramos-Vara, José A., Marilyn E. Beissenherz, Margaret A. Miller, Gayle C. Johnson, John M. Kreeger, Lanny W. Pace, James R. Turk, Susan E. Turnquist, Gary L. Watson, and Ben Yamini. "Immunoreactivity of A103, An Antibody to Melan A, in Canine Steroid-Producing Tissues and their Tumors." Journal of Veterinary Diagnostic Investigation 13, no. 4 (July 2001): 328–32. http://dx.doi.org/10.1177/104063870101300408.

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The monoclonal antibody A103 to the melanocytic differentiation antigen Melan A stains human steroid-producing cells and their tumors. A total of 200 formalin-fixed, paraffin-embedded canine normal tissues and hyperplastic and neoplastic lesions of the adrenal gland, testis, and ovary were immunohistochemically tested for Melan A with antibody A103. Leydig cell tumors (23/23, 100%), Sertoli cell tumors (14/15, 93%), and adrenocortical adenomas (12/13, 92%) were consistently positive. Adrenocortical carcinomas (23/35, 65%) and granulosa cell tumors (10/17, 59%) were less frequently positive. All pheochromocytomas, seminomas, and dysgerminomas were negative. The pattern of staining was cytoplasmic, but nuclear staining was also frequently seen in normal Leydig cells and their tumors. As in human tumors, immunohistochemistry for Melan A stains many canine steroid-producing tumors and can be used to distinguish these tumors from those of nonstereidogenic cells.

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Mackensen, Andreas, Norbert Meidenbauer, Sandra Vogl, Monika Laumer, Jana Berger, and Reinhard Andreesen. "Phase I Study of Adoptive T-Cell Therapy Using Antigen-Specific CD8+ T Cells for the Treatment of Patients With Metastatic Melanoma." Journal of Clinical Oncology 24, no. 31 (November 1, 2006): 5060–69. http://dx.doi.org/10.1200/jco.2006.07.1100.

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Purpose The adoptive transfer of in vitro generated tumor antigen-specific cytotoxic T lymphocytes (CTL) provides a promising approach to the immunotherapy of cancer. A phase I study was conducted to test the feasibility, safety, and survival of adoptively transferred Melan-A–specific CTL lines in melanoma patients. Patients and Methods Eleven HLA-A2+ patients with metastatic melanoma received at least three intravenous infusions of Melan-A–specific CTL at 2-week intervals. CTL were generated by four rounds of in vitro stimulation of purified CD8+ peripheral blood lymphocytes with autologous dendritic cells pulsed with an HLA-A2 binding Melan-A peptide. Each T-cell infusion was accompanied by a 6-day course of low-dose interleukin-2. Results A total of 52 T-cell infusions were administered, averaging 2.1 × 108 Melan-A–specific CTL per infusion. Clinical adverse effects were mild and consisted of chills and low-grade fever in seven of 11 patients. Clinical and immunologic responses revealed an antitumor response in three of 11 patients (one complete regression, one partial regression, one mixed response), an elevated frequency of circulating Melan-A tetramer+ T cells up to 2 weeks in all the patients with a maximal frequency of 2% of total CD8+ T cells, an increase in eosinophils to up to 50% in seven of 11 patients, and a selective loss of Melan-A expression in lymph node metastases in two evaluated patients after T-cell transfer. Conclusion Our data indicate that the adoptive transfer of antigen-specific T cells in melanoma patients can induce clinical tumor-specific immune responses without major adverse effects.

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Roma, Andres A., Cristina Magi-Galluzzi, and Ming Zhou. "Differential Expression of Melanocytic Markers in Myoid, Lipomatous, and Vascular Components of Renal Angiomyolipomas." Archives of Pathology & Laboratory Medicine 131, no. 1 (January 1, 2007): 122–25. http://dx.doi.org/10.5858/2007-131-122-deommi.

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Abstract Context.—Renal angiomyolipoma is a tumor composed of varying amounts of fat, smooth muscle, and blood vessels. Characteristically, tumor cells express melanocytic markers such as HMB-45 and Melan-A. Recently, several other markers have been described as having excellent diagnostic sensitivity in cutaneous melanocytic lesions. Objectives.—To compare the sensitivities of 5 melanocytic markers in renal angiomyolipoma and to study the expression patterns of these markers in the 3 different components of angiomyolipoma. Design.—A tissue microarray of 20 renal angiomyolipomas was constructed. For each case, 3 cores containing fat, blood vessels, and smooth muscle were taken. The tissue microarray was then stained for HMB-45, Melan-A, tyrosinase, NK1-C3, and CD117. Results.—HMB-45 was positive in 95%, Melan-A in 85%, NK1-C3 in 70%, tyrosinase in 50%, and CD117 in 40% of the cases. All (20/20) were positive for HMB-45 and Melan-A combined. These 5 markers had different sensitivities in the 3 components. HMB-45 was positive in 90%, 85%, and 80% of fat, smooth muscle, and blood vessel components, respectively; Melan-A in 70%, 60%, and 40%; NK1-C3 in 55%, 55%, and 45%; tyrosinase in 30%, 40%, and 10%; and CD117 in 20%, 40%, and 10%, respectively, of these 3 components. Conclusions.—HMB-45 and Melan-A combined were positive in 100% of the renal angiomyolipomas. We recommend the use of these 2 markers in the workup of this entity, including those with predominantly 1 component. Other melanocytic markers are of limited use. A tissue block comprising predominantly fat or smooth muscle components should be used when performing melanocytic marker immunostain.

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Beleaua, Marius-Alexandru, Ioan Jung, Cornelia Braicu, Doina Milutin, and Simona Gurzu. "SOX11, SOX10 and MITF Gene Interaction: A Possible Diagnostic Tool in Malignant Melanoma." Life 11, no. 4 (March 27, 2021): 281. http://dx.doi.org/10.3390/life11040281.

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Malignant melanoma (MM) is a highly heterogenic tumor whose histological diagnosis might be difficult. This study aimed to investigate the diagnostic and prognostic utility of the conventional pan-melanoma cocktail members (HMB-45, melan-A and tyrosinase), in conjunction with SOX10 and SOX11 immunohistochemical (IHC) expression. In 105 consecutive cases of MMs and 44 of naevi, the IHC examination was performed using the five-abovementioned markers, along with microphthalmia transcription factor (MITF), S100, and Ki67. Correlation with the clinicopathological factors and a long-term follow-up was also done. Survival analysis was performed with Kaplan–Meier curves and compared with TCGA public datasets. None of the 44 naevi expressed SOX11, but its positivity was seen in 52 MMs (49.52%), being directly correlated with lymphovascular invasion, the Ki67 index, and SOX10 expression. HMB-45, SOX10, and tyrosinase, but not melan-A, proved to differentiate the naevi from MMs successfully, with high specificity. Triple MITF/SOX10/SOX11 co-expression was seen in 9 out of 15 negative conventional pan-melanoma-cocktail cases. The independent prognostic value was proved for the conventional pan-melanoma cocktail (triple positivity for HMB-45, melan-A, and tyrosinase) and, independently for HMB-45 and tyrosinase, but not for melan-A, SOX10, or SOX11. As consequence, to differentiate MMs from benign naevi, melan-A should be substituted by SOX10 in the conventional cocktail. Although the conventional pan-melanoma cocktail, along with S100 can be used for the identification of melanocytic origin of tumor cells and predicting prognosis of MMs, the conventional-adapted cocktail (triple positivity for HMB-45, SOX10, and tyrosinase) has a slightly higher diagnostic specificity. SOX11 can be added to identify the aggressive MMs with risk for lymphatic dissemination and the presence of circulating tumor cells.

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Anichini, Andrea, Alessandra Molla, Roberta Mortarini, Gabrina Tragni, Ilaria Bersani, Massimo Di Nicola, Alessandro M. Gianni, et al. "An Expanded Peripheral T Cell Population to a Cytotoxic T Lymphocyte (Ctl)-Defined, Melanocyte-Specific Antigen in Metastatic Melanoma Patients Impacts on Generation of Peptide-Specific Ctls but Does Not Overcome Tumor Escape from Immune Surveillance in Metastatic Lesions." Journal of Experimental Medicine 190, no. 5 (September 6, 1999): 651–68. http://dx.doi.org/10.1084/jem.190.5.651.

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It is not known if immune response to T cell–defined human histocompatibility leukocyte antigen (HLA) class I–restricted melanoma antigens leads to an expanded peripheral pool of T cells in all patients, affects cytotoxic T lymphocyte (CTL) generation, and correlates with anti-tumor response in metastatic lesions. To this end, a limiting dilution analysis technique was developed that allowed us to evaluate the same frequency of peptide-specific T cells as by staining T cells with HLA–peptide tetrameric complexes. In four out of nine patients, Melan-A/Mart-127–35–specific CTL precursors (CTLp) were ≥1/2,000 peripheral blood lymphocytes and found mostly or only in the CD45RO+ memory T cell subset. In the remaining five patients, a low (<1/40,000) peptide-specific CTLp frequency was measured, and the precursors were only in the CD45RA+ naive T cell subset. Evaluation of CTL effector frequency after bulk culture indicated that peptide-specific CTLs could be activated in all patients by using professional antigen-presenting cells as dendritic cells, but CTLp frequency determined the kinetics of generation of specificity and the final number of effectors as evaluated by both limiting dilution analysis and staining with HLA-A*0201–Melan-A/Mart-1 tetrameric complexes. Immunohistochemical analysis of 26 neoplastic lesions from the nine patients indicated absence of tumor regression in most instances, even in patients with an expanded peripheral T cell pool to Melan-A/Mart-1 and whose neoplastic lesions contained a high frequency of tetramer-positive Melan-A/Mart-1–specific T cells. Furthermore, frequent lack of a “brisk” or “nonbrisk” CD3+CD8+ T cell infiltrate or reduced/absent Melan-A/Mart-1 expression in several lesions and lack of HLA class I antigens were found in some instances. Thus, expansion of peripheral immune repertoire to Melan-A/Mart-1 takes place in some metastatic patients and leads to enhanced CTL induction after antigen-presenting cell–mediated selection, but, in most metastatic lesions, it does not overcome tumor escape from immune surveillance.

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Bennett, D. C., P. J. Cooper, T. J. Dexter, L. M. Devlin, J. Heasman, and B. Nester. "Cloned mouse melanocyte lines carrying the germline mutations albino and brown: complementation in culture." Development 105, no. 2 (February 1, 1989): 379–85. http://dx.doi.org/10.1242/dev.105.2.379.

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We have established two new immortal lines of mouse melanocytes, melan-b and melan-c, from mice homozygous for the brown (b) and albino (c) mutations respectively. Both lines were derived through differentiation in vitro of embryonic epidermal melanoblasts. The brown melanocytes are visibly brown by light microscopy, and centrifuged cell suspensions form brown pellets. The albino melanocytes form white pellets and contain abundant unpigmented premelanosomes as shown by transmission electron microscopy. Like normal, non-immortal melanocytes and like the immortal black melanocyte line melan-a, both lines show little or no growth in a standard, serum-supplemented medium, but proliferate well in the presence of 12-o-tetradecanoyl phorbol-13-acetate (TPA). Sustained growth of the albino cells also requires either keratinocyte feeder cells or 2-mercaptoethanol (2-ME). The modal chromosome numbers are 39 for melan-b and 40 (diploid) for melan-c. Neither line is tumorigenic in nude mice. Heterokaryons between the two lines can be constructed and form wild-type, black pigment. Melanocyte lines can now be reproducibly generated from mice of different strains, and provide tools for molecular studies of germline coat-colour mutations. These two lines provide elegant means to study the developmentally controlled expression of the two complementary genes, B and C, with black melanin pigment as a readily detectable natural marker.

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Romano, Emanuela, Helene Bichat, Athina Stravodimou, Pedro Romero, Speiser E. Daniel, Frederic Triebel, Olivier Michielin, Alexander Harari, and Serge Leyvraz. "Effect of Melan-Α/Μart-1-peptide vaccination plus IMP321 on antitumor immunity and clinical benefit in patients receiving autologous PBMCs after lymphodepletion." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e20011-e20011. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e20011.

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e20011 Background: Immunotherapy offers great promise for cancer treatmet. Strong evidence supports adoptive cell transfer (ACT) and immunemodulation for regression of advanced melanoma. Few studies assessed the potential synergy between these two strategies. Methods: Twelve patients with metastatic melanoma received multiple Melan-A/Mart-1-peptide vaccinations with (n=6) or without (n=6) IMP321 (LAG-3Ig fusion protein) as an adjuvant in combination with lymphodepleting chemotherapy and ACT. All patients were selected on the basis of ex vivo detectable Melan-A-specific CD8 T cell responses and were immunized at day (D) 0, 8, 15, 22, 28, 52, and 74 post-reinfusion. Results: One-week after reinfusion of bulk autologous PBMCs, a significant expansion of Melan-A-specific CD8 T cells was measured in >83% (n=5) and <17% (n=1) of patients from the IMP321 and control groups, respectively (p=0.02). Compared to the control group, the mean fold increase of Melan-A-specific CD8 T cells was respectively >2-, >4-, and >6-fold higher in the IMP321 group at D15, D30, and D60 (p=0.02). A long-lasting Melan-A-specific CD8 T-cell response was significantly associated with IMP321 (p<0.001). A higher proportion of Melan-A-specific CD8 TEMRA (i.e., CD45RA+CCR7-CD127-) cells was observed in the IMP321 group at the peak of the response (p <0.002), whereas no significant difference was observed in the expression of co-inhibitory receptors (i.e., PD-1, 2B4, TIM3, CD160). IMP321 was associated with a significantly (p<0.04) reduced expansion of regulatory T cells (TREGS); we observed a negative correlation between the fold increase of Melan-A-specific CD8 T cells and the relative expansion of TREGS. Clinical benefit (assessed as CR, PR, and SD) was observed in none of the control patients vs 67% (4/6) of patients from the IMP321 group, (p=0.02). Conclusions: Vaccination with IMP321 as an adjuvant in combination with lymphodepleting chemotherapy and ACT provided clinical benefit and this was associated with a more robust and durable cellular antitumor immune response, supporting further development of IMP321 for future immunotherapeutic strategies. Clinical trial information: NCT00324623.

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Maize,, John C., Jack S. Resneck,, Philip E. Shapiro, Timothy H. McCalmont, and Philip E. LeBoit. "Ducking Stray “Magic Bullets”: A Melan-A Alert." American Journal of Dermatopathology 25, no. 2 (April 2003): 162–65. http://dx.doi.org/10.1097/00000372-200304000-00013.

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Colombetti, Sara, Theres Fagerberg, Petra Baumgärtner, Laurence Chapatte, Daniel E. Speiser, Nathalie Rufer, Olivier Michielin, and Frédéric Lévy. "Impact of Orthologous Melan-A Peptide Immunizations on the Anti-Self Melan-A/HLA-A2 T Cell Cross-Reactivity." Journal of Immunology 176, no. 11 (May 18, 2006): 6560–67. http://dx.doi.org/10.4049/jimmunol.176.11.6560.

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Tucker, A. R., and J. R. Smith. "Prostatic Squamous Metaplasia in a Cat with Interstitial Cell Neoplasia in a Retained Testis." Veterinary Pathology 45, no. 6 (November 2008): 905–9. http://dx.doi.org/10.1354/vp.45-6-905.

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An 11-year-old cat with a retained testis was presented with a chronic history of dysuria and bladder atony. Medical therapy failed to alleviate the clinical signs. Contrast radiography demonstrated a diffusely narrowed urethra. During a celiotomy and prepubic urethrostomy, a retained testis, stenosed urethra, and irregularly enlarged prostate were observed. Histopathologic diagnosis was retained testis with a well-differentiated interstitial cell tumor, a poorly differentiated interstitial cell tumor, and marked squamous metaplasia of the prostatic epithelium with suppurative prostatitis. Neoplastic interstitial cells were immunoreactive for Melan A, consistent with reports of Melan A expression in steroid hormone-producing tissue. This is the first report of prostatic squamous metaplasia associated with testicular neoplasia in a felid.

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Pavlick, Anna C., Ana Blazquez, Marcia Meseck, Michael J. Donovan, Mireia Castillo-Martin, Tin Htwe Thin, Rachel Sabado, et al. "A phase II open labeled, randomized study of poly-ICLC matured dendritic cells for NY-ESO-1 and Mean-A peptide vaccination compared to Montanide, in melanoma patients in complete clinical remission." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 9538. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.9538.

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9538 Background: Dendritic cells (DC) play a critical role in tumor immune-surveillance. Combination therapies by utilizing check point inhibitors may revert tumor-induced-T cell exhaustion; however, DCs are necessary to prime/activate T cells to target tumor cells. Montanide is a mineral oil-based adjuvant that enhances the immune response to vaccination. In this study, we compared the immunogenicity of Montanide and poly-ICLC-matured DCs. Methods: This is a Phase II open label, randomized two arm study to compare Poly-ICLC matured DC with systemic administration of Poly-ICLC on days 1 and 2 (ARM A) to Montanide ISA-51 and Poly-ICLC as adjuvants for NY-ESO-1 and Melan-A/MART-1 peptide vaccination with systemic administration of Poly-ICLC on day 2 (ARM B) in study subjects with melanoma in complete clinical remission but at high risk of disease recurrence (NCT02334735). Evaluation of primary tumor expression of NY-ESO-1 and Melan-A tumor was determined by immunohistochemistry (IHC). Humoral responses were assessed by Seromics (ELISA) and T-cell responses were performed ex-vivo by interferon (IFN)-g enzyme-linked immunospot assay (ELISPOT) and after expansion by intracellular cytokine staining (ICS). Results: Twenty-nine patients have been enrolled in this study. IHC studies demonstrated tumor expression of NY-ESO-1 and Melan-A in 78% and 81% of the patients, respectively. 100% of patients within arm B became seropositive for NY-ESO-1 peptide by cycle 2 day 8 (C2D8). 80% of patients within arm A also seroconverted to this antigen but titers were significantly lower. Melan-A-specific antibody responses were also found in arm B patients, but to a lesser degree. However, arm A patients failed to develop seroreactivity to Melan-A. Cellular responses are under analysis. Preliminary data show that subjects in both arms develop T cell responses to both antigens. Conclusions: This vaccine trial reached the primary endpoint of safety and tolerability. Patients vaccinated with either DC or Montanide had demonstrable antibody titers to immunizing antigens, although the latter reproducibly induced higher titers. Evaluation of cellular responses is ongoing. Clinical trial information: NCT02334735.

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Nicholson, Donald. "Poem: A genetic ode, or a melan coli tale." Biochemistry and Molecular Biology Education 33, no. 3 (May 2005): 217. http://dx.doi.org/10.1002/bmb.2005.494033032482.

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Mackensen, Andreas, Norbert Meidenbauer, Sandra Vogl, Monika Laumer, and Reinhard Andreesen. "Adoptive T Cell Therapy Using Antigen-Specific CD8+ T Cells for the Treatment of Patients with Cancer: A Phase I Clinical Study." Blood 106, no. 11 (November 16, 2005): 2393. http://dx.doi.org/10.1182/blood.v106.11.2393.2393.

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Abstract The adoptive transfer of in vitro induced and expanded tumor antigen-specific cytotoxic T lymphocytes (CTL) provides a promising approach to the immunotherpy of cancer. We have previously shown that antigen-specific CTL can be generated from HLA-A2.1+ cancer patients by 4 rounds of in vitro stimulation of purified CD8+ T cells with autologous dendritic cells pulsed with HLA-A2 binding tumor-associated peptides. Based on these results we have initiated a pilot study of adoptive T cell therapy in advanced melanoma patients demonstrating that in vitro generated Melan-A (ELAGIGILTV)-specific CTL survive intact in vivo for several weeks and localize preferentially to tumor. Here we report on the clinical results of a phase I study of 11 HLA-A2+ melanoma patients that received at least three i.v. infusions of Melan-A-specific CTL i.v. at 2-week intervals. Each T cell infusion was accompanied by a 6-day course of s.c. IL-2 (3x106 IU daily). A total of 51 T-cell infusions were administered, averaging 2.1 x108 Melan-A specific T cells per infusion, with a range from 0.11 – 13.1 x108 T cells per infusion. Clinical side effects were mild and consisted of chills and low-grade fever (WHO grade I–II) in 7 out of 11 patients that typically occurred within 6 to 8 h post infusion. Hematological effects, observed after T cell transfer, included an increase in eosinophils up to 50% in 7 out of 11 patients, peaking 24h post transfer. Clinical and immunological responses consisted of antitumor responses in 3 out of 11 patients (1 CR, 1 PR, 1 mixed response), an elevated frequency of circulating Melan-A multimer+ T cells up to 2% of total CD8+ T cells for 2 weeks post T cell infusion, suggesting long-term survival and/or proliferation of transferred CTL, and a complete loss of Melan-A expression in lymph node metastases of 2 patients after T cell transfer. Our data indicate that the adoptive transfer of antigen-specific T cells in cancer patients is capable of inducing clinical and systemic tumor-specific immune responses without provoking major side effects.

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Peterson, Amy C., Helena Harlin, and Thomas F. Gajewski. "Immunization With Melan-A Peptide-Pulsed Peripheral Blood Mononuclear Cells Plus Recombinant Human Interleukin-12 Induces Clinical Activity and T-Cell Responses in Advanced Melanoma." Journal of Clinical Oncology 21, no. 12 (June 15, 2003): 2342–48. http://dx.doi.org/10.1200/jco.2003.12.144.

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Purpose: Preclinical studies showed that immunization with peripheral blood mononuclear cells (PBMC) loaded with tumor antigen peptides plus interleukin-12 (IL-12) induced CD8+ T-cell responses and tumor rejection. We recently determined that recombinant human (rh) IL-12 at 30 to 100 ng/kg is effective as a vaccine adjuvant in patients. A phase II study of immunization with Melan-A peptide-pulsed PBMC + rhIL-12 was conducted in 20 patients with advanced melanoma. Patients and Methods: Patients were HLA-A2–positive and had documented Melan-A expression. Immunization was performed every 3 weeks with clinical re-evaluation every three cycles. Immune responses were measured by ELISpot assay before and after treatment and through the first three cycles, and were correlated with clinical outcome. Results: Most patients had received prior therapy and had visceral metastases. Nonetheless, two patients achieved a complete response, five patients achieved a minor or mixed response, and four patients had stable disease. The median survival was 12.25 months for all patients and was not yet reached for those with a normal lactate dehydrogenase. There were no grade 3 or 4 toxicities. Measurement of specific CD8+ T-cell responses by direct ex vivo ELISpot revealed a significant increase in interferon gamma–producing T cells against Melan-A (P = .015) after vaccination, but not against an Epstein-Barr virus control peptide (P = .86). There was a correlation between the magnitude of the increase in Melan-A–specific cells and clinical response (P = .046). Conclusion: This immunization approach may be more straightforward than dendritic cell strategies and seems to have clinical activity that can be correlated to a biologic end point.

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Sánchez, J., G. A. Ramirez, A. J. Buendia, M. Vilafranca, C. M. Martinez, J. Altimira, and J. A. Navarro. "Immunohistochemical Characterization and Evaluation of Prognostic Factors in Canine Oral Melanomas with Osteocartilaginous Differentiation." Veterinary Pathology 44, no. 5 (September 2007): 676–82. http://dx.doi.org/10.1354/vp.44-5-676.

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Melanomas are the most common malignant oral neoplasm in dogs. Osteocartilaginous differentiation in oral melanomas is a rare feature described both in veterinary and human medicine. Here, 10 cases of this type of neoplasm were used to study their immunohistochemical, biological, and clinical characteristics. Reactivity for S100 and melan A antigen was evaluated, and 4 prognosis factors (mitotic index, invasiveness of epithelium, nuclear atypia, and proliferation index) were analyzed and correlated with the clinical course of the neoplasms after diagnosis. Immunohistochemical analysis of the studied neoplasms, including the osteocartilaginous areas, showed positive immunoreaction for S100 and melan A, except in one dog, which was negative for melan A. Analysis of the results showed that oral melamonas with osteocartilaginous differentiation have a clinical course similar to that of other melanomas in the oral cavity. Analysis of the mitotic index and the expression of proliferation marker Ki-67 could be useful tools for predicting the biological behavior of these neoplasms.

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Makhlouf, Hala R., Kamal G. Ishak, Raj Shekar, Isabell A. Sesterhenn, Denise Y. Young, and Julie C. Fanburg-Smith. "Melanoma Markers in Angiomyolipoma of the Liver and Kidney." Archives of Pathology & Laboratory Medicine 126, no. 1 (January 1, 2002): 49–55. http://dx.doi.org/10.5858/2002-126-0049-mmiaot.

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Abstract Context.—Melanoma markers, especially the new microphthalmia transcription factor (mitf), have not been previously compared in hepatic and renal angiomyolipomas. Objectives.—To evaluate expression of the novel melanocytic markers mitf and tyrosinase in angiomyolipomas, and to compare these markers with the established markers HMB-45 and melan-A in both hepatic and renal tumors. Design.—Clinical, histopathologic, and immunohistochemical features of 15 hepatic angiomyolipomas were compared with those of 10 renal angiomyolipomas. Results.—No significant differences between patients with hepatic angiomyolipomas and renal angiomyolipomas were found with respect to age, gender, race, and tumor size. Hepatic angiomyolipomas exhibited a predominance of the epithelioid smooth muscle cell component, in contrast to their renal counterparts, which were predominantly spindled. The smooth muscle cells expressed HMB-45 in 100% of cases in both groups, melan-A in 14 of 15 hepatic angiomyolipomas and 8 of 9 renal angiomyolipomas, mitf in 5 of 12 hepatic angiomyolipomas versus 6 of 10 renal angiomyolipomas, and tyrosinase in 3 of 12 and 2 of 10 hepatic angiomyolipomas and renal angiomyolipomas, respectively. The extent and intensity of immunostaining with HMB-45 and melan-A were dependent on whether spindled or epithelioid cells predominated; the epithelioid cells showed stronger and more widespread reactivity than the spindled cells. Conclusion.—We believe that the best immunohistochemical marker for confirming the diagnosis of angiomyolipoma is HMB-45, followed by melan-A. Routine use of mitf and/or tyrosinase is not indicated.

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Tamura, Kanako, Norihiko Ohbayashi, Yuto Maruta, Eiko Kanno, Takashi Itoh, and Mitsunori Fukuda. "Varp Is a Novel Rab32/38-binding Protein That Regulates Tyrp1 Trafficking in Melanocytes." Molecular Biology of the Cell 20, no. 12 (June 15, 2009): 2900–2908. http://dx.doi.org/10.1091/mbc.e08-12-1161.

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Two small GTPase Rabs, Rab32 and Rab38, have recently been proposed to regulate trafficking of melanogenic enzymes to melanosomes in mammalian epidermal melanocytes; however, the exact molecular mechanism of Rab32/38-mediated transport of melanogenic enzymes has never been clarified, because no Rab32/38-specific effector has ever been identified. In this study, we screened for a Rab32/38-specific effector by a yeast two-hybrid assay using a guanosine triphosphate (GTP)-locked Rab32/38 as bait and found that VPS9-ankyrin-repeat protein (Varp)/Ankrd27, characterized previously as a guanine nucleotide exchange factor (GEF) for Rab21, functions as a specific Rab32/38-binding protein in mouse melanocyte cell line melan-a. Deletion analysis showed that the first ankyrin-repeat (ANKR1) domain functions as a GTP-dependent Rab32/38-binding domain, but that the N-terminal VPS9 domain (i.e., Rab21-GEF domain) does not. Small interfering RNA-mediated knockdown of endogenous Varp in melan-a cells caused a dramatic reduction in Tyrp1 (tyrosinase-related protein 1) signals from melanosomes but did not cause any reduction in Pmel17 signals. Furthermore, expression of the ANKR1 domain in melan-a cells also caused a dramatic reduction of Tyrp1 signals, whereas the VPS9 domain had no effect. Based on these findings, we propose that Varp functions as the Rab32/38 effector that controls trafficking of Tyrp1 in melanocytes.

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Danga, Mary Elizabeth, Ron Yaar, and Jag Bhawan. "Melan-A positive dermal cells in malignant melanomain situ." Journal of Cutaneous Pathology 42, no. 6 (April 14, 2015): 388–93. http://dx.doi.org/10.1111/cup.12473.

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Creytens, David. "Melan A Antibody Cross-Reactivity in Molluscum Contagiosum Bodies." International Journal of Surgical Pathology 26, no. 2 (August 14, 2017): 151–52. http://dx.doi.org/10.1177/1066896917725805.

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Leinweber, Bernd, Rainer Hofmann-Wellenhof, Steven Kaddu, and Timothy H. McCalmont. "Procollagen 1 and Melan-A Expression in Desmoplastic Melanomas." American Journal of Dermatopathology 31, no. 2 (April 2009): 173–76. http://dx.doi.org/10.1097/dad.0b013e3181930b85.

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Siniard, Wesley C., Matthew F. Sheley, Brittany N. Stevens, Christine A. Parker-Graham, Melissa A. Roy, Devinn M. Sinnott, Katherine D. Watson, et al. "Immunohistochemical analysis of pigment cell tumors in two cyprinid species." Journal of Veterinary Diagnostic Investigation 31, no. 5 (July 22, 2019): 788–91. http://dx.doi.org/10.1177/1040638719864380.

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Pigment cell tumors, also known as chromatophoromas, are cutaneous spindle cell neoplasms originating from pigment cells (chromatophores) in the dermis of teleosts, amphibians, and reptiles. Chromatophoromas share similar histologic morphology to other spindle cell tumors and are not always pigmented. Therefore, immunohistochemical analysis may be useful in distinguishing these neoplasms from tumors of other cellular origin when poorly pigmented. We performed 3 immunohistochemistry assays (PNL-2, melan A, and SOX10) on 8 cutaneous neoplasms from 8 teleosts diagnosed as chromatophoromas based on histologic morphology. Semiquantitative analysis of immunoreactivity was evaluated on each immunohistochemical assay using a 0–3 scale. PNL-2 exhibited mild-to-moderate (1 or 2) immunoreactivity in 7 of the cases, and resident chromatophores (internal control) were also immunoreactive in these cases. Melan A exhibited mild-to-moderate (1 or 2) immunoreactivity in 4 cases (and with resident chromatophores in these cases); SOX10 was not immunoreactive in any cases. Our results indicate that PNL-2 may be a useful marker in teleosts to distinguish tumors of chromatophore origin. Melan A could also be useful, but appears to be less sensitive, and SOX10 is likely not a useful marker for these neoplasms in teleosts.

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Khordadmehr, M., S. Jarolmasjed, J. Ashrafi-Helan, and R. Naebzadeh. "Unusual ocular Hodgkinʼs-like lymphoma in a dog." BULGARIAN JOURNAL OF VETERINARY MEDICINE 23, no. 3 (2020): 389–93. http://dx.doi.org/10.15547/bjvm.2241.

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Hodgkin’s disease is a malignant lymphoproliferative disease with various gross morphology. The present paper reports gross and microscopic features of Hodgkinʼs-like lymphoma in a dog. An eight years-old dog was presented to our hospital due to complete blindness associated with the presence of proliferative tissue on the globe surface. The tissue biopsy sample was soft and frigid with high bleeding tendency and was processed for histopathological evaluation. Sections of 5 μm in thickness were stained with haematoxylin-eosin and melan-A and S-100 by immunohistochemistry (IHC) for differential diagnosis with ocular melanoma. Histologically, regarding the negative Melan-A and S100 IHC findings, and particular histological features, a mixed cellularity type of Hodgkin’s disease which included a large number of lymphocytes with different size and shape together with single necrosis was diagnosed. Additionally, Reed-Sternberg cells which had a deeply lobulated nucleus were demonstrated.

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Kim, J., H. Shin, and J. Park. "RNA in Salivary Extracellular Vesicles as a Possible Tool for Systemic Disease Diagnosis." Journal of Dental Research 96, no. 8 (April 14, 2017): 938–44. http://dx.doi.org/10.1177/0022034517702100.

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Saliva contains biological information as blood and is recognized as a valuable diagnostic medium for their noninvasiveness. Although “-omics” researches have tried to investigate saliva, the origin and significance of its contents are not clear, and its usage is largely confined to oral disease in the diagnostic and prognostic field. In an attempt to broaden the applicability of saliva and to find systemic disease-derived RNA in saliva, we made mouse models that had human melanoma and isolated extracellular vesicles (EVs) from their saliva by an aqueous 2-phase system (ATPS), then identified and evaluated their expression of human melan-A RNA, which is associated with melanoma on skin. With ATPS, EVs were isolated efficiently and stably while taking less time compared to isolation by ultracentrifugation. When ATPS was used to isolate EVs from saliva, the mean ± SD percentage of EVs recovered from initial EVs was 38.22% ± 18.55% by the number of particles, and the mean ± SD percentage of RNA recovered from the initial amount was 60.33% ± 5.34%. RNAs within isolated EVs were analyzed subsequently by reverse transcription quantitative polymerase chain reaction and polymerase chain reaction from saliva and plasma. In melanoma mice, amplification of human melan-A was identified from saliva and plasma, even though a relative amount of normalized melan-A was lower than that of plasma. These results present a possibility that RNAs derived from systemic disease are transferred into saliva from blood in EVs. Also, they suggest that saliva could be exploited in obtaining information about systemic disease, not only about oral disease, by examining RNAs in EVs from saliva instead of blood.

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GUO, HAIYING, KE YANG, FANG DENG, YIZHAN XING, YUHONG LI, XIAOHUA LIAN, and TIAN YANG. "Wnt3a inhibits proliferation but promotes melanogenesis of melan-a cells." International Journal of Molecular Medicine 30, no. 3 (June 14, 2012): 636–42. http://dx.doi.org/10.3892/ijmm.2012.1028.

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An, Yun Ah, Ji Yeon Hwang, Jae Soon Lee, and Young Chul Kim. "Cornus officinalis Methanol Extract Upregulates Melanogenesis in Melan-a Cells." Toxicological Research 31, no. 2 (June 30, 2015): 165–72. http://dx.doi.org/10.5487/tr.2015.31.2.165.

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Tiwari, Raj, Jan Geliebter, Alberta Lucchese, Abraham Mittelman, and Darja Kanduc. "Computational peptide dissection of Melan-a/MART-1 oncoprotein antigenicity." Peptides 25, no. 11 (November 2004): 1865–71. http://dx.doi.org/10.1016/j.peptides.2004.07.004.

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Fernandes, Bruno F., Alexandre N. Odashiro, Vinicius S. Saraiva, Patrick Logan, Emilia Antecka, and Miguel N. Burnier. "Immunohistochemical expression of melan-A and tyrosinase in uveal melanoma." Journal of Carcinogenesis 6, no. 1 (2007): 6. http://dx.doi.org/10.1186/1477-3163-6-6.

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Baek, Seung-hwa, and Sang-Han Lee. "Omeprazole inhibits melanin biosynthesis in melan-a cells and zebrafish." Experimental Dermatology 25, no. 3 (February 10, 2016): 239–41. http://dx.doi.org/10.1111/exd.12915.

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Hwang, Jeong-Ah, Myeong-Jin Goh, Eun-Joo Kim, Myong-Ryul Lee, Nok-Hyun Park, Yong-Joo Na, Jun-Cheol Cho, and Hae-Kwang Lee. "Identification of Sake Extract as a New Anti-melanogenic Ingredient by in vitro and Clinical Trials." Natural Product Communications 8, no. 11 (November 2013): 1934578X1300801. http://dx.doi.org/10.1177/1934578x1300801126.

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Overproduction of melanin is the cause of skin hyperpigmentation, which is related to several skin diseases and cosmetic concerns. Sake is a Japanese alcoholic beverage produced from rice and water by fermentation, but is little known for its effect on melanogenesis. To identify the effect of sake extract on melanin synthesis, a melanin assay was performed in melan-A murine melanocytes. Sake extract treatment significantly inhibited melanin production in a dose-dependent manner, and tyrosinase, the rate-limiting enzyme of melanogenesis, decreased significantly at the protein level. Further investigations were performed with multiple assay systems; a sake extract reduced melanin production in melan-A/SP-1 murine cell co-culture, and also in MelanoDermTM, a skin equivalent model of human keratinocytes-melanocytes. Finally, subjects were treated with a formula containing the sake extract. Topical application of the sake extract product improved skin lightness (L*) significantly within 7 days. We identified sake extract as a new anti-melanogenic ingredient through in vitro and in vivo experiments. These results suggest that a sake extract can be used to improve skin hyperpigmentation.

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Vignard, Virginie, Brigitte Lemercier, Annick Lim, Marie-Christine Pandolfino, Yannick Guilloux, Amir Khammari, Catherine Rabu, et al. "Adoptive Transfer of Tumor-Reactive Melan-A-Specific CTL Clones in Melanoma Patients Is Followed by Increased Frequencies of Additional Melan-A-Specific T Cells." Journal of Immunology 175, no. 7 (September 21, 2005): 4797–805. http://dx.doi.org/10.4049/jimmunol.175.7.4797.

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Cheung, Florence Wing-Ki, Albert Wing-Nang Leung, Wing Keung Liu, and Chun-Tao Che. "Tyrosinase Inhibitory Activity of a Glucosylated Hydroxystilbene in Mouse Melan-a Melanocytes." Journal of Natural Products 77, no. 6 (June 16, 2014): 1270–74. http://dx.doi.org/10.1021/np4008798.

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Williams, S. M., G. Zavala, S. Hafner, S. R. Collett, and S. Cheng. "Metastatic Melanomas in Young Broiler Chickens (Gallus gallus domesticus)." Veterinary Pathology 49, no. 2 (August 8, 2011): 288–91. http://dx.doi.org/10.1177/0300985811415706.

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Four young broiler chickens affected by multiple melanotic tumors are described. Grossly, there were multiple tumors composed of melanocytes within the skin, skeletal muscle, and multiple visceral organs. Tumors ranged from flattened macules to masses that extensively replaced viscera. Microscopically, melanocytes were often well pigmented, and while there was moderate nuclear anisokaryosis, mitotic rates were low. Immunohistochemical staining of some melanomas with antibodies to S100 proteins, Melan-A, vimentin, or neuron-specific enolase after bleaching of tumor cells with potassium permanganate revealed lack of immunostaining of tumor cells with antibodies to S100, strong positive staining of tumor cells for neuron-specific enolase, moderate staining with antibodies to vimentin, and faint staining for Melan-A. Only neuron-specific enolase staining was evident in unbleached tumor cells. Attempts to identify exogenous avian leukosis viruses in these tumors were unsuccessful.

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Fusi, A., A. Busse, S. Ochsenreither, A. Rietz, and U. Keilholz. "Expression of stem cell markers in circulating melanoma cells." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e22056-e22056. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e22056.

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e22056 Background: Within circulating tumor cells there may be a subset of cell with stem cell (tumor initiating) characteristics able to develop distant metastasis. Several markers including nestin and CD133 have been found to be possible candidates to identify such a kind of subpopulation in other experimental models. We evaluated the presence of melanoma cells bearing stem cell phenotype in the bloodstream of patients with cutaneous or uveal melanoma after depletion of the leukocytes fraction. Methods: Between 50 and 100 ml of peripheral blood were collected from 12 melanoma patients with various tumor burden as well as three healthy volunteers. Blood samples were enriched for tumour cells by CD45 depletion of the leukocyte fraction using magnetic beads separation (EasySep, Stem Cell Technologies. Inc.). The remaining material was stained with antibodies for the markers Melan-A/Mart-1 (Dako) and HMB45 (Dako), CD133 (Miltenyi Biotec) and nestin (R&D System) and analysed by flow cytometry (BD FACSCalibur). Ten ml of blood were further processed and CD133, nestin, Melan-A/Mart-1 transcripts were quantified by Real Time RT-PCR (LightCycler, Roche Diagnostic). Results: CD45-depleted fractions in healthy controls were negative for melanoma markers. Melan-A/Mart-1 and/or HMB45 positive cells were detectable in 11 out of 12 melanoma patients. The absolute number of melanoma cells identified ranged from 6 to 176 per 10 ml of blood. Nestin expressing cells were more represented compared to CD133 expressing cells (median 27.4%, range 0.3% to 65.1% vs. median 9.3%, range 0.1% to 16.8%) within the melanoma fraction of cells positive for Melan-A/Mart-1 and/or HMB45. In one patient two different melanoma cell populations were detectable. The population of cells with lower expression of the melanoma markers showed at the same time higher expression of nestin and CD133 (5.9% vs. 1.3% and 10.2% vs. 6.7% respectively). Nestin results were in good accordance to the FACS data (nestin: r=0.55; CD133: r=0.23; Pearson test). Conclusions: The novel negative separation technique allows reliable isolation of melanoma cells from peripheral blood of patients with metastatic disease. A significant fraction of melanoma cells in peripheral blood bears a stem cell phenotype. No significant financial relationships to disclose.

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Ramos-Vara, J. A., M. A. Miller, G. C. Johnson, S. E. Turnquist, J. M. Kreeger, and G. L. Watson. "Melan A and S100 Protein Immunohistochemistry in Feline Melanomas: 48 Cases." Veterinary Pathology 39, no. 1 (January 2002): 127–32. http://dx.doi.org/10.1354/vp.39-1-127.

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Journal articles on the topic 'Melan-A'

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