Background. p63 expression in Merkel cell carcinoma (MCC) indicates an aggressive behaviour of the tumour. At least three TA variants (TAp63α,β,γ) and three ΔN variants (ΔNp63α,β,γ) by alternative splicing from p63 gene have been identified. Recently it has been suggested that presence of polyomavirus (MCPyV) in MCC tumour tissue is an indicator of adverse prognosis. 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 45 patients collected from different Institutions. Methods. 50 cases of MCC from 45 patients (6 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 value the p63 gene status. The presence of MCPyV in the MCC tumour genome was also investigated by PCR in all cases. Results. p63 expression was detected in 62% of cases by IHC and it was associated with decreasing overall survival (p = 0.003). All these cases but one presented at least one of the p63 isoforms by RT-PCR, both in the primary MCC (25 cases) and in metastases (5 cases), with a variable expression pattern of the isoforms (TAp63γ was present in 76.7% of cases, ΔNp63β in 16.7%, ΔNp63α in 36.7%, TAp63β in 16.7%, TAp63γ in 6.7%, ΔNp63γ in 3.3%). P63 gene gain was found by FISH analysis in only one case. Clonal integration of MCV DNA sequences was observed in 86.6% of cases. The present IHC and molecular data confirm p63 expression in a group of MCC with aggressive clinical behaviour and suggest that a transcriptional dysregulation of p63 gene is involved in the pathogenesis of MCC. IHC analysis is less specific than the molecular analysis to value p63 expression in MCC. Clonal integration of MCPyV DNA sequences does not seem related to prognosis.
Expression of P63 in merkel cell carcinoma is related to prognosis: an immunohistochemical and molecular analysis
ASIOLI, SOFIA;DE BIASE, DARIO;MORANDI, LUCA;
2010
Abstract
Background. p63 expression in Merkel cell carcinoma (MCC) indicates an aggressive behaviour of the tumour. At least three TA variants (TAp63α,β,γ) and three ΔN variants (ΔNp63α,β,γ) by alternative splicing from p63 gene have been identified. Recently it has been suggested that presence of polyomavirus (MCPyV) in MCC tumour tissue is an indicator of adverse prognosis. 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 45 patients collected from different Institutions. Methods. 50 cases of MCC from 45 patients (6 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 value the p63 gene status. The presence of MCPyV in the MCC tumour genome was also investigated by PCR in all cases. Results. p63 expression was detected in 62% of cases by IHC and it was associated with decreasing overall survival (p = 0.003). All these cases but one presented at least one of the p63 isoforms by RT-PCR, both in the primary MCC (25 cases) and in metastases (5 cases), with a variable expression pattern of the isoforms (TAp63γ was present in 76.7% of cases, ΔNp63β in 16.7%, ΔNp63α in 36.7%, TAp63β in 16.7%, TAp63γ in 6.7%, ΔNp63γ in 3.3%). P63 gene gain was found by FISH analysis in only one case. Clonal integration of MCV DNA sequences was observed in 86.6% of cases. The present IHC and molecular data confirm p63 expression in a group of MCC with aggressive clinical behaviour and suggest that a transcriptional dysregulation of p63 gene is involved in the pathogenesis of MCC. IHC analysis is less specific than the molecular analysis to value p63 expression in MCC. Clonal integration of MCPyV DNA sequences does not seem related to prognosis.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
