Melanoma biomarker expression in melanocytic tumor progression: a tissue microarray study

Abstract

The elucidation of protein biomarkers that are differentially expressed in human melanocytic tumors during tumor progression may lead to the identification of therapeutic targets and novel diagnostic tests. In a meeting chaired by Dr Mihm, a list of biomarkers of interest in melanoma was compiled. The specialized programs of research excellence (SPORE) in skin cancer developed a melanocytic tumor progression tissue microarray (TMA) to evaluate these candidate biomarkers. In addition to markers reported elsewhere, we evaluated c-Kit, MITF, MART1, HMB-45 and bcl-2. The TMA contains 480 cores of benign nevi, primary cutaneous melanoma and melanoma metastases. Immunohistochemical detection of melanoma biomarkers, including c-Kit, MITF, MART-1, HMB-45 and bcl-2 was performed. Intense nuclear staining for MITF protein was observed in 83% of nevi, 56% of primary melanomas and 23% of metastases. Bcl-2 expression was reduced with progression to metastasis (detected in 86, 89 and 52% of nevi, primaries and metastases, respectively), contrary to MART-1, which showed no differential expression (74, 85 and 84%). HMB-45 was observed in 18% of nevi and most (72 and 75%) primary melanomas and metastases. c-Kit protein increased with progression from nevi to primary tumor (10 and 77% of cases, respectively) and was decreased in metastases (26% of cases). Through a collaboration of the Skin SPOREs sponsored by the Organ Systems Branch of the National Cancer Institute (NCI), we identified a list of melanoma biomarkers of interest, developed a melanocytic tumor progression TMA and completed a coordinated analysis of these biomarkers. This TMA has served as a powerful validation tool for newly identified and known melanoma biomarkers by revealing trends in expression during tumor progression and by confirming the heterogeneity of biomarker expression in cutaneous melanocytic tumors.