Expression of γ-H2AX in endometrial carcinomas: an immunohistochemical study with p53

OBJECTIVE.: The most frequently mutated gene in human cancer is p53, a gene that functions in the checkpoint response to DNA double-strand breaks. γ-H2AX is a marker of activated DNA damage and is overexpressed in many malignancies and their precursor lesions. The purpose of this study was to evaluate the association between p53 and γ-H2AX expression and the clinical value of γ-H2AX in endometrial carcinoma. METHODS.: We investigated 106 patients with primary endometrial carcinoma (type I/endometrioid, n=84; type II/non-endometrioid, n=20; mixed pattern or other histological types, n=2) who were treated at our institution between 1999 and 2009. γ-H2AX and p53 expression were assessed using immunohistochemistry from paraffin-embedded tissue blocks, and results were correlated with clinical data. RESULTS.: A strong positive correlation was observed between γ-H2AX and p53 expression (p<0.0001). Like p53, γ-H2AX staining was significantly associated with advanced tumor stage (p=0.04), histological grade (p<0.0001), histological type (p<0.0001), and vascular space involvement (p=0.05), but not with lymph node involvement (p=0.64) and patients' age (p=0.36). In a univariate survival analysis, p53 and γ-H2AX staining were associated with a shortened disease-free and overall survival but in the Cox regression analyses both parameters did not serve as independent prognostic parameter. CONCLUSIONS.: Our findings suggest that there is a link between the p53 dependent cell cycle arrest and γ-H2AX dependent DNA repair pathway in endometrial cancer. Increasing expression levels of γ-H2AX are associated with unfavourable prognostic factors in type I and type II endometrial carcinomas.