Reduced expression of BAX is associated with poor prognosis in patients with epithelial ovarian cancer: a multifactorial analysis of TP53, p21, BAX and BCL-2

Abstract

Summary Traditional clinicopathological features do not predict which patients will develop chemotherapy resistance. The TP53 gene is frequently altered in ovarian cancer but its prognostic implications are controversial. Little is known on the impact of TP53-downstream genes on prognosis. Using molecular and immunohistochemical analyses we examined TP53 and its downstream genes p21, BAX and BCL-2 in ovarian tumour tissues and have evaluated the results in relation to clinico-pathological parameters, clinical outcome and response to platinum-based chemotherapy. Associations of tested factors and patient and tumour characteristics were studied by Spearman rank correlation and Pearsons χ 2 test. The Cox proportional hazard model was used for univariate and multivariate analysis. The associations of tested factors with response was tested using logistic regression analysis. TP53 mutation, p21 and BCL-2 expression were not associated with increased rates of progression and death. Expression of TP53 was associated with a shorter overall survival only (relative hazard rate [RHR] 2.01, P = 0.03). Interestingly, when combining TP53 mutation and expression data, this resulted in an increased association with overall survival (P = 0.008). BAX expression was found to be associated with both progression-free (RHR 0.44, P = 0.05) and overall survival (RHR 0.42, P = 0.03). Those patients who simultaneously expressed BAX and BCL-2 had a longer progression-free and overall survival compared to patients whose tumours did not express BCL-2 (P = 0.05 and 0.015 respectively). No relations were observed between tested factors and response to platinum-based chemotherapy. We conclude that BAX expression may represent a prognostic indicator for patients with ovarian cancer and that the combined evaluation of BAX and BCL-2 may provide additional prognostic significance.

The clinicopathological significance of Bax and Bcl-2 protein expression with tumor infiltrating lymphocytes in ovarian carcinoma

“…In our study, the mucinous, clearcell and endometrial carcinomas tended to have higher Bax expression level, whereas the serous, mucinous, mixed and clear-cell subtypes had a tendency to have lower Bcl-2 expression level. As was shown in several previous studies, Bcl-2 and Bax expression was not associated with histologic type and grade in our study [20,21].…”

Evaluation of clinical significance of TP53, BCL-2, BAX and MEK1 expression in 229 ovarian carcinomas treated with platinum-based regimen

“…In subgroups related to the TP53 status, BCL-2 and BAX demonstrated an influence on CR or DFS, which was not seen in all tumours. Among other studies evaluating predictive significance of BCL-2 (Herod et al, 1996;Mano et al, 1999;Schuyer et al, 2001), including two published by Baekelandt et al (1999Baekelandt et al ( , 2000 on a comparable number of ovarian carcinomas, only Mano et al (1999) noticed higher frequency of CR in patients with BCL-2 negative tumours.…”

“…In regard to BAX expression, a few studies have addressed the issue of its clinical significance in advanced stage ovarian carcinomas; however, associations with CR or DFS have not been observed (Marx et al, 1997;Baekelandt et al, 2000;Sengupta et al, 2000;Schuyer et al, 2001). Recently, Schuyer et al (2001) found an association of BAX expression with progression-free survival.…”

“…Recently, Schuyer et al (2001) found an association of BAX expression with progression-free survival.…”

“…The strong impact of clinical parameters on clinical end points in our analysis is in agreement with other studies (Makar et al, 1995;Partridge et al, 1996;Eisenhauer et al, 1999). Usually, immunohistochemical markers present lower associations with clinical end points than clinical parameters (Diebold et al, 1996;Herod et al, 1996;Baekelandt et al, 1999Baekelandt et al, , 2000Mano et al, 1999;Geisler et al, 2000;Reles et al, 2001;Schuyer et al, 2001). In our analysis, the only exception was the positive influence of high BAX expression on DFS in patients with TP53-positive ovarian carcinomas -it was stronger than that of the FIGO stage.…”