Molecular assessment of allelic loss in Warthin tumors

Abstract

Warthin's tumors are benign lesions of the head and neck that have a characteristic morphologic appearance. The etiology of Warthin's tumors is controversial and whether they are true neoplasms or developmental malformations continues to be debated. In this study, we examined 12 Warthin tumors with a molecular and immunohistochemical approach. Immunostains for p53 and p16ink were performed. The epithelial and lymphoid components of each lesion were microdissected and PCR was performed for 13 microsatellite markers at or near common tumor suppressor genes. The results were analyzed semiquantitatively using capillary electrophoresis. Frequency of allelic loss was calculated. The epithelial component of all tumors was negative for p53 and p16ink. By molecular genotyping there was only one case that had one locus with allelic imbalance, while the remainder had no evidence of clonal allelic loss. The immunohistochemical and molecular results in this study lend support to the hypothesis that Warthin tumors are non-neoplastic, as there was no evidence of aberrant staining for tumor suppressor gene protein products and no evidence of consistent clonal allelic losses. Modern Pathology (2005) 18, 964-968.

Fluorescence in situ hybridization for detection of MAML2 rearrangements in oncocytic mucoepidermoid carcinomas: utility as a diagnostic test

“…These are essentially tumors of the elderly, prevalent in the sixth to seventh decade with a male predilection and strong smoking association. It is not even certain that Warthin tumors are true clonal neoplasms [28,29]. Some evidence indicates that Warthin tumors have a high prevalence of the "common" 4977-base pair deletion, a marker of oxidative stress and senescence [30,31].…”

Bilateral and multifocal Warthin�s tumor of parotid gland: two case reports and review of literature

“…Various theories about its histogenesis have been proposed, two of them are most commonly agreed. The first theory asserts that Warthin's tumor could be an atypical parotid adenoma in which an inflammatory response has caused an extensive lymphocytic infiltration (26,27). The second theory, more absorbing, ascribes to the embryogenesis processes the origins of this disease.…”

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).…”

“…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).…”