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

The putative role of TP53 and p16INK4A tumor suppressor genes and Ras oncogenes in the development and progression of salivarygland neoplasias was studied in 28 cases of pleomorphic adenomas (PA), 4 cases of cystic adenocarcinomas, and 1 case ofcarcinoma ex-PA. Genetic and epigenetic alterations in the above genes were analyzed by Polymerase Chain Reaction/SingleStrand Conformational Polymorphism (PCR/SSCP) and sequencing and by Methylation Specific-PCR (MS-PCR). Mutations in TP53were found in 14% (4/28) of PAs and in 60% (3/5) of carcinomas. Mutations in H-Ras and K-Ras were identified in4%(1/28) and7%(2/28) of PAs, respectively. Only 20% (1/5) of carcinomas screened displayed mutations in K-Ras. p16INK4A promoterhypermethylation was found in 14% (4/28) of PAs and 100% (5/5) carcinomas. All genetic and epigenetic alterations were detectedexclusively in the epithelial and transitional tumor components, and were absent in the mesenchymal parts. Our analysis suggeststhat TP53 mutations and p16INK4A promoter methylation, but not alterations in the H-Ras and K-Ras genes, might be involved in themalignant progression of PA into carcinoma. J. Cell. Physiol. 207: 654–659, 2006. 2006 Wiley-Liss, Inc.