Differential UBE2C and HOXA1 expression in Spitz nevus and melanoma

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 versus Spitz nevi (P=0.003), whereas HOXA1 was down-regulated in melanoma (P<0.0001). Immunohistochemical analysis confirmed increased nuclear expression of UBE2C in melanoma (mean = 18% of cells; range 3–44%) when compared to Spitz nevi (mean = 9%; range 2–28%) (P=0.001) and conventional nevi (mean = 1.5%; range 0–9%) (P<0.0001). Strong UBE2C staining was identified in cells undergoing mitosis. UBE2C RNA and protein detection correlated with mitotic rate (P < 0.0001). On the other hand, HOXA1 nuclear staining was low in melanoma (mean = 69%; range 5 – 100%) when compared to Spitz nevi (mean = 94%; range 66–100%: P=0.0024) and conventional nevi (mean = 94%; range 83–99%; P=0.009).

Conclusions

UBE2C and HOXA1 RNA and protein are differentially expressed in conventional and Spitz nevi and melanoma.

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