Histological Features, p53, c-Kit, and Poliomavirus Status and Impact on Survival in Merkel Cell Carcinoma Patients.

Abstract

Merkel cell carcinoma (MCC) is a rare and aggressive malignancy from neuroendocrine cells in the skin. Despite being one of the most life-threatening of skin cancers, little is known about the potential signaling mechanism that drives carcinogenesis in MCC. The purpose of this study is to assess the impact of Merkel cell polyomavirus (MCPyV), p53, and c-kit on the histological features and clinical prognosis of MCC treated in our regional hospitals. The design was a retrospective study. The specimens were taken between 1993 and 2013 in 2 referral hospitals of Southern Spain. Data were collected retrospectively and analyzed using SPSS software. Thirteen lesions from 13 subjects were included in the study. Positivity for c-kit was associated with the absence of MCPyV viral DNA (P = 0.048) and positivity for p53 (P = 0.002). More rate of mitoses per high-power field was presented significantly in those specimens with: positivity for c-kit (P = 0.046), positivity for p53 (P = 0.05), lesions with infiltrative growth pattern (P = 0.008), and lymphovascular invasion (P = 0.034). We observed an inverse relationship between p53 expression and MCPyV infection (Pearson's coefficient: -0.524; P = 0.046) and between c-kit expression and MCPyV infection (Pearson's coefficient: -0.548; P = 0.05), whereas the relationship was positive between p53 expression and c-kit expression (Pearson's coefficient: 0.884; P < 0.001). We conclude that presence of MCPyV DNA has no effect on overall survival. MCCs with p53 and c-kit expressions are associated with the absence of or low MCPyV DNA showing an inverse relationship. A multifactorial molecular pathogenesis where positivity for p53 and c-kit are associated with other mechanisms different than MCPyV (such as pro-mitotic factors) may lead to aggressive clinical behavior.