TP53 mutations in salivary gland neoplasms

Abstract

Many studies have demonstrated that loss of TP53 gene function has an important role in the genesis of many neoplasms, including salivary gland neoplasms. The purpose of this study was to examine the mutation profile of the TP53 gene in salivary gland neoplasms. Genomic DNA was extracted from paraffin-embedded tissues of pleomorphic adenoma, carcinoma in pleomorphic adenoma, mucoepidermoid carcinoma, adenoid cystic carcinoma and polymorphous low grade adenocarcinoma. Exons 5 to 8 of the TP53 gene were amplified by polymerase chain reaction (PCR) to perform single-stranded conformational polymorphism (SSCP) analysis. Band shifting was observed in exons 5, 6 and 8 in 9 out of 18 neoplasms. The results of this study suggest that mutations in TP53 gene are related to salivary gland neoplasms pathogenesis and that exons 5 and 8 are most frequently involved.

Transformation of pleomorphic adenoma to carcinoma ex pleomorphic adenoma of the parotid gland is independent of p53 mutations

“…Therefore, studies with a larger group of patients are neither practical nor feasible. Most of the published studies were performed with either a small number of patients or various malignant tumors of the salivary glands [10].…”

“…In several studies a loss of p53 function was responsible for the development of cancer [5][6][7]. Alterations of p53 have been reported in a variety of salivary gland tumors [8][9][10].…”

The absence of significant mutational events of the p53 gene in the only two salivary gland tumors possessing radiation-related development risks, mucoepidermoid carcinoma and Warthin tumor

“…This result was not surprising, because the over-expression of p53 has been reported to be specific to lesions with cellular proliferation or malignancy (18)(19)(20)(21)(22)(23)(24)(25). The over-expression of P53 in mucoepidermoid carcinomas has been well documented with its frequencies ranging from 53% to 67% (25,28,(30)(31), while the sequencing data of the p53 gene have been rather limited, showing some sporadic point mutations (27,29,(32)(33). In physiological conditions, p53 gene products are degraded soon after they are targeted to nuclei (39), hence, it is usually hard to detect P53 within a cell by conventional immunohistochemical methods.…”

“…Among the proto-oncogenes, p53 gene has been extensively investigated for its functional changes due to alteration in various kinds of human experimental animal tumors (16)(17). However, there has been a significant amount of information about p53 mutations in salivary gland tumors, and their important role in their pathogeneses has been indicated (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). In addition, there have been a large number of reports on the relationship between frequent p53 mutations and ultraviolet radiation-induced tumorigeneses of human skin squamous cell carcinoma (34) or experimental murine skin tumors (35)(36).…”

Assessment of TP53 mutations in benign and malignant salivary gland neoplasms

“…All these studies relied on either DGGE or SSCP assays, followed by direct sequencing when necessary. Other groups assessed TP53 mutations by performing SSCP analysis alone and observing band shifts in exons 5, 6 and 8 in salivary tumors; however, they did not sequence the samples [26,27]. SSCP can miss mutations detected by direct sequencing.…”