PURPOSE: To investigate the prognostic and predictive relevance of p53, Mdm2, and Bcl-2 protein expression in advanced ovarian cancer. PATIENTS AND METHODS: Tumor biopsy specimens from 185 consecutive and homogeneously treated patients with stage III ovarian cancer were examined immunohistochemically for expression of p53, Mdm2, and Bcl-2 proteins. Both uni- and multivariate analyses of prognostic factors were performed, and correlations with classical clinicopathologic parameters and response to chemotherapy were examined. RESULTS: Forty-nine percent and 39% of cases were considered positive for expression of p53 and Bcl-2, respectively. p53 expression was correlated with loss of histologic differentiation and Bcl-2 expression with smaller residual disease after primary surgery. The absence of p53 expression and the presence of Bcl-2 expression were associated with improved survival but not with overall response to chemotherapy, although a positive correlation was found between Bcl-2 expression and the possibility of obtaining a completely negative second-look laparotomy. Expression of Mdm2 was found in 17% of cases. Although correlations were found with known favorable clinicopathologic factors, no prognostic significance was demonstrated for Mdm2 in this patient group. In multivariate analyses, histologic type, degree of differentiation, residual disease, and p53 alone or combined with Bcl-2 expression were found to be independently associated with overall survival. CONCLUSION: p53, and especially the combination of p53 and Bcl-2 expression data, represents an independent prognostic predictor in stage III ovarian cancer. Despite their role in the apoptotic process, p53 and Bcl-2 do not seem to be clinically useful predictors of response to combination chemotherapy in these patients.
PURPOSE: To investigate the prognostic and predictive relevance of p53, Mdm2, and Bcl-2 protein expression in advanced ovarian cancer. PATIENTS AND METHODS: Tumor biopsy specimens from 185 consecutive and homogeneously treated patients with stage III ovarian cancer were examined immunohistochemically for expression of p53, Mdm2, and Bcl-2 proteins. Both uni- and multivariate analyses of prognostic factors were performed, and correlations with classical clinicopathologic parameters and response to chemotherapy were examined. RESULTS: Forty-nine percent and 39% of cases were considered positive for expression of p53 and Bcl-2, respectively. p53 expression was correlated with loss of histologic differentiation and Bcl-2 expression with smaller residual disease after primary surgery. The absence of p53 expression and the presence of Bcl-2 expression were associated with improved survival but not with overall response to chemotherapy, although a positive correlation was found between Bcl-2 expression and the possibility of obtaining a completely negative second-look laparotomy. Expression of Mdm2 was found in 17% of cases. Although correlations were found with known favorable clinicopathologic factors, no prognostic significance was demonstrated for Mdm2 in this patient group. In multivariate analyses, histologic type, degree of differentiation, residual disease, and p53 alone or combined with Bcl-2 expression were found to be independently associated with overall survival. CONCLUSION:p53, and especially the combination of p53 and Bcl-2 expression data, represents an independent prognostic predictor in stage III ovarian cancer. Despite their role in the apoptotic process, p53 and Bcl-2 do not seem to be clinically useful predictors of response to combination chemotherapy in these patients.
Authors: Andrea Mann; Estrid Hogdall; Susan J Ramus; Richard A DiCioccio; Claus Hogdall; Lydia Quaye; Valerie McGuire; Alice S Whittemore; Mitul Shah; David Greenberg; Douglas F Easton; Bruce A J Ponder; Susanne Krüger Kjaer; Simon A Gayther; Deborah J Thompson; Paul D P Pharoah; Honglin Song Journal: Eur J Cancer Date: 2008-08-22 Impact factor: 9.162
Authors: Elnaz F Firoz; Melanie Warycha; Jan Zakrzewski; Danuta Pollens; Guimin Wang; Richard Shapiro; Russell Berman; Anna Pavlick; Prashiela Manga; Harry Ostrer; Julide Tok Celebi; Hideko Kamino; Farbod Darvishian; Linda Rolnitzky; Judith D Goldberg; Iman Osman; David Polsky Journal: Clin Cancer Res Date: 2009-03-24 Impact factor: 12.531
Authors: Kathleen M Darcy; William E Brady; John W McBroom; Jeffrey G Bell; Robert C Young; William P McGuire; R Ilona Linnoila; Denver Hendricks; Tomas Bonome; John H Farley Journal: Gynecol Oncol Date: 2008-10-02 Impact factor: 5.482
Authors: P de Graeff; A P G Crijns; S de Jong; M Boezen; W J Post; E G E de Vries; A G J van der Zee; G H de Bock Journal: Br J Cancer Date: 2009-06-09 Impact factor: 7.640