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. gamma-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 gamma-H2AX expression and the clinical value of gamma-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. gamma-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 gamma-H2AX and p53 expression (p<0.0001). Like p53, gamma-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 gamma-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 gamma-H2AX dependent DNA repair pathway in endometrial cancer. Increasing expression levels of gamma-H2AX are associated with unfavourable prognostic factors in type I and type II endometrial carcinomas. (C) 2010 Elsevier Inc. All rights reserved.