The significance of p53 mutation and over-expression in ovarian cancer prognosis

Abstract

Mutation of the p53 tumor suppressor gene is the most commonly observed genetic abnormality in human tumors and associations between p53 aberration and patient survival have been shown for several tumor types. Previous studies have found that approximately 50% of epithelial ovarian carcinomas exhibit abnormalities in the p53 gene. The aim of this study, 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, PAb240 and PAb1801, p53 over‐expression was observed in 20/39 (51%) tumors. When these results were combined with previously reported IHC and sequencing analyses, 37/61 (61%) tumors exhibited a p53 aberration. Although there was no significant difference between sequencing and IHC results, several cases gave discordant results, indicating that a combination of both methods may be required to estimate accurately the proportion 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 analysis, 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 FIGO 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 conclusion, p53 mutation and overexpression does not appear to be a significant indicator of patient survival in this series of ovarian carcinomas.

Expression and Mutation of p53 in Tumor Effusion Cells of Patients with Ovarian Carcinoma: Response to Cisplatin-Based Chemotherapy

“…In agreement with earlier reports [19,31,32], our studies showed no significant association between histological grade and p53 overexpression. However, others have shown that p53 aberrations were correlated with poor tumor differentiation [11,12,16,35,39,41]. Similar to our previous observations, a large volume of published data [17,32,35,38,39] indicates that carcinomas showing p53 changes are usually classified as III/IV FIGO stages.…”

“…However, others have shown that p53 aberrations were correlated with poor tumor differentiation [11,12,16,35,39,41]. Similar to our previous observations, a large volume of published data [17,32,35,38,39] indicates that carcinomas showing p53 changes are usually classified as III/IV FIGO stages. Nevertheless, others have been unable to show such relationships [16,19,31,36,40,41].…”

“…However, the trend toward more frequent p53 reactivity in serous adenocarcinomas was visible. In the majority of reports, the highest incidence of p53 accumulation was shown in serous carcinomas [11,16,18,34,35,39,40] while in other studies [17,32,38], no apparent changes in p53 related to histology were found. In agreement with earlier reports [19,31,32], our studies showed no significant association between histological grade and p53 overexpression.…”

Modest effect of p53, EGFR and HER-2/neu on prognosis in epithelial ovarian cancer: a meta-analysis

“…For p53, 62 studies reporting results of 75 analyses in 9448 patients were included (Supplementary Table 3; median study size 102 patients, range 20-783; Hartmann et al, 1994;Klemi et al, 1995;Allan et al, 1996;Eltabbakh et al, 1997;Viale et al, 1997;Darai et al, 1998;Marx et al, 1998;Silvestrini et al, 1998;Anttila et al, 1999;Baekelandt et al, 1999;Kassim et al, 1999;Wen et al, 1999 ). There were 13 prospective studies and 49 retrospective studies.…”

Factors influencing p53 expression in ovarian cancer as a biomarker of clinical outcome in multicentre studies

“…Mutations of the p53 gene as determined by mutation analysis and/or positive immunohistochemical (IHC) staining for p53 are common in ovarian cancer and have been associated with poor clinical outcome. However, results of the many studies on the prognostic value of p53 expression in ovarian cancer are inconclusive (Marks et al, 1991;Hartmann et al, 1994;Van Der Zee et al, 1995;Allan et al, 1996;Anttila et al, 1999;Ferrandina et al, 1999;Reles et al, 2001;Nakayama et al, 2003;Nielsen et al, 2004). One of the most important reasons for these conflicting results is the considerable methodological variability among the different studies (Hall et al, 2004).…”