TP53, BCL-2 and BAX analysis in 199 ovarian cancer patients treated with taxane-platinum regimens

• Published in: Gynecologic oncology Vol. 112; no. 1; pp. 179 - 184
• Main Authors: Ziółkowska-Seta, Izabela, Mądry, Radosław, Kraszewska, Ewa, Szymańska, Teresa, Timorek, Agnieszka, Rembiszewska, Alina, Kupryjańczyk, Jolanta
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2009
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; BAX; BCL-2; bcl-2-Associated X Protein - biosynthesis; Carboplatin - administration & dosage; Cell Line, Tumor; Cisplatin - administration & dosage; Female; Hematology, Oncology and Palliative Medicine; Humans; Immunohistochemistry; Middle Aged; Neoplasm Staging; Obstetrics and Gynecology; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Paclitaxel - administration & dosage; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Taxane-platinum; Taxoids - administration & dosage; TP53; Tumor Suppressor Protein p53 - biosynthesis; Young Adult; BCL-2; BAX; Taxane-platinum; TP53; Ovarian cancer
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2008.09.008

Abstract Objective In cell line studies, BCL-2 and BAX proteins interfere with cancer response to taxanes. This issue has not received much attention with regard to taxane-platinum (TP)-treated ovarian cancer patients. Methods We evaluated prognostic/predictive significance of BCL-2 and BAX with regard to TP53 status. Immunohistochemical analysis was performed on 199 ovarian carcinomas FIGO stage IIB–IV treated with TP; the results were analyzed by the Cox and logistic regression models. Results Clinicopathological parameters (residual tumor size, FIGO stage and/or tumor grade, but not patient's age) were the only or the strongest predictors of patient's outcome. Platinum highly sensitive response showed a positive association with TP53 accumulation ( p = 0.045). As in our previously published analysis on platinum-cyclophosphamide-treated group, complete remission showed a borderline negative (paradoxic) association with high BAX expression in the whole group ( p = 0.058) and with BCL-2 expression in the TP53(−) group ( p = 0.058). Conclusion Our results suggest that TP53, BCL-2 and BAX proteins carry some predictive potential in taxane-platinum-treated ovarian cancer patients, auxiliary to clinicopathological factors. We have confirmed on another patient group that clinical importance of BCL-2 may depend on TP53 status.