Objective: To investigate the role of ataxia telangiectasis mutated (ATM) gene in the oncogenesis and progression of oral squamous cell carcinoma (OSCC).
Methods: A total of 61 formalin-fixed and paraffin-embedded samples were obtained from patients with hyperkeratosis, oral leukoplakia, OSCC and normal healthy controls. The expression of ATM protein in all of the samples was investigated by streptavidin-peroxidase immunohistochemistry assay. PCR was also performed to detect the loss of heterozygosity (LOH) in D11s2179 of ATM gene. The correlations between ATM and the clinical and histopathological characteristics were also investigated.
Results: The results indicated that the ATM expression was increased in oral premalignant lesions (P<0.05). For OSCC, 68.8% samples showed normal or increased ATM expression, while 31.3% had decreased or absent ATM expression. Significant differences were found between the group of decreased or absent ATM expression and that of normal or increased expression over the histopathological grade and lymph node metastasis state. PCR results displayed that none of the samples from oral premalignant lesions showed abnormal changes, while 3 of the OSCC (9.38%) showed loss of heterozygosity (LOH) and 2 (6.25%) with microsatellite instability (MSI). Those 3 samples of LOH showed absent ATM expression.
Conclusion: These findings indicated that the over expression of ATM may contribute to prevent carcinogenesis of OSCC. ATM inactivation may be one of the genetic alterations of the molecular progression of OSCC.