Expression of DNA doublestrand repair proteins in oral leukoplakia and the risk of malignant transformation

The present study assessed the expression of the DNA doublestrand repair (DDR) proteins ATM serine/threonine kinase (ATM), checkpoint kinase 2 (CHEK2) and gamma H2A histone family member X (gamma H2AFX) in oral leukoplakia (OL) and evaluated their clinical significance and usefulness as biomarkers for predicting OL transformation. Retrospectively, ATM, CHEK2 and gamma H2AFX protein levels were evaluated using immunohistochemical analysis in 61 OL, 33 oral squamous cell carcinoma (OSCC) and 15 normal oral mucosa tissues. OL tissues were classified into two groups according to the epithelial dysplasia pathology: The low risk dysplasia group (n=41) and the high-risk dysplasia group (n=20). The results of the present study revealed that the expression of ATM and gamma H2AFX in OSCC was significantly increased compared with that in OL with low-risk dysplasia and normal oral mucosa tissues. There was no statistically significant difference in CHEK2 expression among the groups. ATM expression was correlated with that of gamma H2AFX in OSCC tissue. The prognostic values of the DDR proteins and their correlation with clinical and pathological parameters were evaluated further in 99 OL patients with low risk dysplasia. Multivariate analysis revealed that increased expression of ATM and gamma H2AFX was significantly associated with an increased risk of malignant transformation. Immunohistochemical analysis of ATM and gamma H2AFX protein expression provided useful prognostic information on the carcinogenesis of OL. Increased ATM and gamma H2AFX expression may indicate a poor prognosis.