Coarse melanin in human melanoma

Yale University, New Haven CT

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Abstract

A clinical feature of primary cutaneous melanoma is variegate pigmentation, yet little is known of its cellular basis. Clark (1977) observed melanoma cells with "melanin deposited in a coarsely granular fashion, commonly seen in vertical phase melanomas". The purpose of this study was to investigate these coarse melanin structures and their potential role in melanoma progression. Archival biopsies of primary and metastatic melanomas were surveyed for coarse melanin-containing melanoma cells and characterized through immunohistochemistry. In 14 of 18 cases of primary vertical phase tumors, coarse melanin structures were found in hypermelanotic areas in both melanoma cells and melanophages. The structures had a characteristic glycosylation pattern of beta 1-6 branched N-glycans, detected by staining with the lectin LPHA. They also stained with HMB45 and anti-CD63 (phagolysosomal membrane component. Thus, coarse melanin was associated with phagolysosomal membrane component). Thus, coarse melanin was associated with phagolysosomal vesicles having melanosomal components. Further, similar vesicles were detected in non-melanized melanomas, staining positively for LPHA, HMB45, and CD63, yet lacking melanin.. Since betaI-6 branched N-glycans are highly correlated with metastasis, and are indicators of poor prognosis in breast and colon carcinomas, the possibility is raised that these LPHA-staining melanoma cells may be involved in metastatic progression. Consistent with this, an initial survey of archival melanoma metastases revealed an abundance of cells with coarse melanin vesicles. The purpose of this study is to expand our initial observations to a larger cohort of primary and metastatic melanomas, matched from individual patients, to determine the prevalence and distribution of such vesicles in melanoma.