TP53 and p16INK4A, but not H-KI-Ras, are involved in tumorigenesis and progression of pleomorphic adenomas

✍ Scribed by Claudia Augello; Valter Gregorio; Viviana Bazan; Patrizia Cammareri; Valentina Agnese; Sandra Cascio; Simona Corsale; Valentina Calò; Arianna Gullo; Rita Passantino; Grazia Gargano; Loredana Bruno; Gaetana Rinaldi; Vincenza Morello; Aldo Gerbino; Rosa Maria Tomasino; Marcella Macaluso; Eva Surmacz; Antonio Russo

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 169 KB
• Volume: 207
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.20601

✦ Synopsis

Abstract

The putative role of TP53 and p16^INK4A^ tumor suppressor genes and Ras oncogenes in the development and progression of salivary gland neoplasias was studied in 28 cases of pleomorphic adenomas (PA), 4 cases of cystic adenocarcinomas, and 1 case of carcinoma ex‐PA. Genetic and epigenetic alterations in the above genes were analyzed by Polymerase Chain Reaction/Single Strand Conformational Polymorphism (PCR/SSCP) and sequencing and by Methylation Specific‐PCR (MS‐PCR). Mutations in TP53 were found in 14% (4/28) of PAs and in 60% (3/5) of carcinomas. Mutations in H‐Ras and K‐Ras were identified in 4% (1/28) and 7% (2/28) of PAs, respectively. Only 20% (1/5) of carcinomas screened displayed mutations in K‐Ras. p16^INK4A^ promoter hypermethylation was found in 14% (4/28) of PAs and 100% (5/5) carcinomas. All genetic and epigenetic alterations were detected exclusively in the epithelial and transitional tumor components, and were absent in the mesenchymal parts. Our analysis suggests that TP53 mutations and p16^INK4A^ promoter methylation, but not alterations in the H‐Ras and K‐Ras genes, might be involved in the malignant progression of PA into carcinoma. © 2006 Wiley‐Liss, Inc.