To identify cancer-related genes that are involved in the carcinogenesis of extramammary Paget's disease (EMPD), we compared mRNA expression profiles of EMPD lesions and corresponding normal skin using cDNA array. Sixty-eight genes were highly expressed (>5-fold) in EMPD lesions compared to normal skin, and 40 genes were expressed less than one-fifth in EMPD lesions. Among them, PIG7/LITAF mRNA was overexpressed in 3 of 4 EMPD cases. PIG7/LITAF transcription is induced by p53 expression and has been implicated in the p53-induced apoptotic pathway. Since expression of p53 mRNA and p53 protein was not high in any of the 3 EMPD samples compared to the intact skin of the same patient, we analyzed PIG7/LITAF cDNA mutations among 12 EMPD samples (including the former 4) by PCR-SSCP. Three samples showed shifted bands (2 had point mutations leading to amino acid substitutions and 1 had a silent mutation). One sample with amino acid substitution overexpressed PIG7/LITAF mRNA in cDNA array analysis and RT-PCR. PIG7/LITAF mRNA expression is confined to tumor cells in in situ mRNA hybridization analysis. These results indicate that genetic disorder and overexpression of PIG7/LITAF may be involved in EMPD carcinogenesis.
Copyright 2004 Wiley-Liss, Inc.