Differential UBE2C and HOXA1 expression in melanocytic nevi and melanoma

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Abstract
Background: Recent molecular advances suggest that Spitz nevi and other spitzoid neoplasms are biologically distinct from melanoma and conventional nevi. The ubiquitin ligase UBE2C and the homeobox transcription factor HOXA1 are candidate oncogenes in melanoma.Methods: Using RNA expression analysis and immunohistochemistry, we evaluated these biomarkers in Spitz nevi (n = 20), melanoma (n = 20), and by immunohistochemistry in conventional nevi (n = 20).Results: RNA analysis with branched DNA multiplex assay identified upregulation of UBE2C in melanomas vs Spitz nevi (P = .003), whereas HOXA1 was downregulated in melanoma (P < .0001). Immunohistochemical analysis confirmed increased nuclear expression of UBE2C in melanoma (mean = 18% of cells; range 3%‐44%) when compared with Spitz nevi (mean = 9%; range 2%‐28%; P = .001) and conventional nevi (mean = 1.5%; range 0‐9%; P < .0001). Strong UBE2C staining was identified in cells undergoing mitosis. UBE2C RNA and protein detection correlated with mitotic rate (P < .0001). On the other hand, HOXA1 nuclear staining was low in melanoma (mean = 69%; range 5%‐100%) when compared with Spitz nevi (mean = 94%; range 66%‐100%; P = .0024) and conventional nevi (mean = 94%; range 83%‐99%; P = .009).Conclusions: UBE2C and HOXA1 RNA and protein are differentially expressed in conventional and Spitz nevi and melanoma.
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  • Massachusetts General Hospital

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