P63 EXPRESSION AS A NEW PROGNOSTIC MARKER IN MERKEL CELL CARCINOMA.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin tumor, mostly affecting elderly individuals. Histogenesis of this rare tumor as well as prognostic criteria are a matter of dispute. Several prognostic indicators have been proposed for MCC. Gender (male), tumour size >5 cm or > 2 cm, location in the buttock, thigh, trunk or head & neck, advanced clinical stage, small cell size, high mitotic index, diffuse pattern as well as mutation of TP53 gene family, have all been reported as indicators of poor prognosis. The p63 protein is a member of the p53 family, and it can be frequently amplified and/or overexpressed in human tumours including carcinoma of head & neck, lung, skin, esophagus, mammary glands, urothelia, cervix, prostate glands, oral squamous cell carcinomas and in odontogenic tumours. Although p63 per se is not general indicator of poor prognosis, nevertheless it is often associated to poorly differentiated basaloid carcinoma. Recently Fukushima et al. suggested that p63 expression is a disadvantageous factor for prognosis in a subgroups of B-cell lymphomas. Our study will show that the same statement can be made in MCC. METHODS: An immunohistochemical analysis of markers of proliferation (Ki67/MIB1), neuroendocrine differentiation (chromogranin A and synaptophisin) and basal cell differentiation (p63) was performed in a series of 47 cases of MCC. Significance of pathological data and of immunoreactivity with different markers was evaluated by chi-squared test. Survival curves were calculated by Kaplan-Meyer method. The difference of survival was estimated using Wilcoxon or Mantel-Cox test. RESULTS: Immunohistochemical evidence of neuroendocrine differentiation and immunopositivity for cytokeratin 20 were observed in all cases, while p63 positivity (10 of neoplastic cell) was detected in approximately half (25/47; 53.2%) of the cases. Cases positive for p63 showed a more aggressive clinical course than the negative ones (Z =2.93; P=.0003; HR=22.22). CONCLUSIONS: Our data indicate that p63 expression is associated with a worse prognosis in MCC and it represents a new independent marker of clinical evolution with a better predictive power than the other prognostic parameters.