THE SIGNIFICANCE OF P53 MUTATION AND OVER-EXPRESSION IN OVARIAN-CANCER PROGNOSIS

Mutation of the p53 tumor suppressor gene is the most commonly observe d genetic abnormality in human tumors and associations between p53 abe rration and patient survival have been shown for several tumor types. Previous studies have found that approximately 50% of epithelial ovari an carcinomas exhibit abnormalities in the p53 gene. The aim of this s tudy, therefore, was to examine the potential prognostic significance of aberrant p53 in patients with primary epithelial ovarian carcinoma, Using immunohistochemistry (IHC) and the anti-p53 antibodies CM1, PAb 240 and PAb1801, p53 over-expression was observed in 20/39 (51%) tumor s. When these results were combined with previously reported IHC and s equencing analyses, 37/61 (61%) tumors exhibited a p53 aberration. Alt hough there was no significant difference between sequencing and IHC r esults, several cases gave discordant results, indicating that a combi nation of both methods may be required to estimate accurately the prop ortion of tumors with p53 aberrations. Univariate statistical analysis showed that p53 aberrations were significantly associated with tumor grade 3/4, FIGO stage III/IV, serous tumors and the presence of bulk ( >2 cm) residual disease following surgery. In univariate survival anal ysis, tumor grade and stage, ascites and post-surgical residual tumor >2 cm were associated with both overall survival (OS) and disease-free survival (DFS). p53 status, however, was not a predictor of either OS or DFS. Using the Cox proportional hazards model, only PICO stage and post-surgical residual disease >2 cm had an independent effect on OS and only stage was found to be an independent predictor of DFS. In con clusion, p53 mutation and overexpression does not appear to be a signi ficant indicator of patient survival in this series of ovarian carcino mas.