Abstract
Penile carcinoma is a rare disease, accordingly there are few studies on molecular changes, and these results also vary greatly. A total of 26 penile squamous cell carcinomas in Japanese men were studied with respect to HPV, p53 alterations, and methylation of gene promoter region. HPV-DNA was detected in three of 26 patients (11.5%). Overexpression of p53 was observed in 13 of 26 patients (50%), and p53 gene mutations were detected in four of 26 patients (15.4%). The frequency of methylation was as follows: DAPK, 26.9% (7/26); FHIT, 88.4% (23/26); MGMT, 19.2% (5/26); p14, 3.8% (1/26); p16, 23.1% (6/26); RAR-beta, 23.1% (6/26); RASSF1A, 11.5% (3/26); and RUNX3, 42.3% (11/26). As for correlation between HPV and p53 alterations, and methylation status, mutations of the p53 gene were detected only in HPV-negative patients, and methylation was more frequently found in HPV-negative than in HPV-positive patients. The present results suggest that the majority of penile squamous cell carcinomas in Japanese men are unrelated to HPV, and gene alterations accumulate more frequently in HPV-unrelated penile carcinomas.
MeSH terms
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Acid Anhydride Hydrolases / genetics
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Acid Anhydride Hydrolases / metabolism
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Carcinoma, Squamous Cell / genetics*
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Carcinoma, Squamous Cell / pathology
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Carcinoma, Squamous Cell / virology
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Core Binding Factor Alpha 3 Subunit / genetics
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Core Binding Factor Alpha 3 Subunit / metabolism
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Cyclin-Dependent Kinase Inhibitor p16
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DNA Methylation*
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DNA, Viral / analysis*
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Death-Associated Protein Kinases
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Gene Expression Regulation, Neoplastic
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Gene Silencing
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Humans
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Male
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Mutation
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Papillomaviridae / genetics*
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Papillomaviridae / isolation & purification
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Papillomavirus Infections
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Penile Neoplasms / genetics*
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Penile Neoplasms / pathology
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Penile Neoplasms / virology
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Receptors, Retinoic Acid / genetics
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Receptors, Retinoic Acid / metabolism
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Tumor Suppressor Protein p53 / metabolism*
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism
Substances
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Apoptosis Regulatory Proteins
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Biomarkers, Tumor
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CDKN2A protein, human
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Core Binding Factor Alpha 3 Subunit
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Cyclin-Dependent Kinase Inhibitor p16
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DNA, Viral
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Neoplasm Proteins
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RASSF1 protein, human
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Receptors, Retinoic Acid
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Runx3 protein, human
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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fragile histidine triad protein
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retinoic acid receptor beta
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Death-Associated Protein Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Acid Anhydride Hydrolases