p63 Expression in Merkel Cell Carcinoma Is Related to Prognosis: An Immunohistochemical and Molecular Analysis
A Righi, S Asioli, D de Biase, L Morandi, M Ragazzi, L Verdun di Cantogno, C Botta, V Eusebi, G Bussolati. Turin University, Italy; Bologna University, Italy
Background: p63 expression in Merkel cell carcinoma (MCC) indicates an aggressive behavior of the tumor. At least three TA variants (TAp63α,β,γ) and three ΔN variants (ΔNp63α,β,γ) by alternative splicing from p63 gene have been identified. In addition recently it has been suggested that presence of polyomavirus (MCPyV) in MCC tumor tissue is an indicator of adverse prognosis. Therefore, to better define the role of p63 and its variants in MCC and the possible relation to MCPyV, we examined a series of MCC from one single institution.
Design: 18 cases of MCC from 15 patients (2 cases showed nodal metastases and 1 case brain metastasis) were investigated for p63 expression by immunohistochemistry (IHC) and by reverse-transcription polymerase chain reaction (RT-PCR) using isoform-specific primers to evaluate the p63 mRNA expression patterns. Probes for p63 gene (3q28) were used for FISH analysis to evaluate the p63 gene status. The presence of MCPyV in the MCC tumor genome was also investigated by PCR in all cases.
Results: p63 expression was detected in 11/18 (61%) cases using IHC and p63 positivity was associated with decreasing overall survival (p=0.003). All these 11 cases presented at least one of the p63 isoforms, both in the primary MCC (8 cases) and in metastases (3 cases), with a variable expression pattern of the isoforms: TAp63α was detected in 7/11 cases, ΔNp63β in 3/11 cases and ΔNp63α in 1/11 case. No p63 gene amplification was found by FISH analysis. All these patients died of disease after average follow-up of 31 months (range: 2-142 months). The remaining 7 cases of MCC, showing negativity for p63 at IHC, did not display any p63 isoform in 5 cases while 2 cases showed only ΔNp63 isoforms with different C-terminals (α and γ, respectively). Four of the patients are alive without disease, 2 died of other causes and one is alive with nodal metastasis. The average follow-up was 42 months (range: 8-67 months). Clonal integration of MCPyV DNA sequences was observed in all cases.
Conclusions: The present IHC and molecular data confirm p63 expression in a group of MCC with aggressive clinical behavior and suggest that a transcriptional dysregulation of p63 gene is involved in the pathogenesis of MCC. IHC analysis is less sensitive than the molecular analysis to value p63 expression in MCC cases. Clonal integration of MCPyV DNA sequences does not seem related to prognosis.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 85, Wednesday Afternoon