Abstract
Abstract Objectives: PARP, poly(adenosine diphosphate-ribose) polymerase, is a damage sensing protein that is essential to the repair of DNA single-strand breaks. P53 acts as a “genome guardian” molecule that in response to DNA damage mediates cell cycle arrest or induces apoptosis. PARP and p53 function synergistically in repairing DNA damage and suppressing chromosomal rearrangements. The aim of this study was to determine the expression of PARP and p53 in epithelial ovarian cancer (EOC) and correlate with clinico-pathologic characteristics. Methods: PARP and p53 was examined using immuno-histochemistry applied on a tissue microarray of 189 EOC. PARP and p53 expression were examined in relation to clinco-pathologic variables, including age of diagnosis, stage, grade, histologic type, optimal debulking, progression free survival and overall survival. Progression free survival and overall survival were estimated by Kaplan-Meier method, and statistical significance was calculated by the log-rank test. Results: PARP expression was demonstrated in 61% (115/189) of specimens and 99/185 (54%) samples exhibited p53 staining. PARP positive tumors tended to have higher grade (P = 0.03) and complete response to initial treatment (P = 0.009). Patients with positive p53 staining tended to have higher stage of disease (P = 0.004) and there was a trend of patients with positive p53 and weak PARP expression to increase the likelihood of disease progression (OR 2.25 (CI 0.389-13)). The median follow-up was 40 months. However, there were no significant associations between PARP and p53 expression. There was no significant difference in disease free or overall survival for PARP or p53. Conclusion: This study indicates that PARP and p53 are upregulated in EOC with higher grade tumors and more advanced stages, respectively, and may serve as a marker of aggressive disease behavior. Additional studies are warranted to evaluate the role of PARP and p53 expression as a predictor of response to initial treatment, and to identify patients that may benefit from alternative treatments in the adjuvant setting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 803.
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