ISPO

TP53, MEK1, XIAP, BCL-2 and BAX as prognostic and predictive factors in ovarian carcinomas treated with platinum-based regimen.

J Kupryjanczyk, MD a,b, T Szymanska, MD a, R Madry, MD c, G Karpinska, MD b, A Rembiszewska, MSc a, A Timorek, MD b, I Ziolkowska, MD a, J Stelmachow, MD b, J Zielinski MD a, J Markowska, MD c

a Departments of Molecular Biology and Gynecologic Oncology, Oncology Center, Warsaw, b Departments of Pathology and Obstetrics and Gynecology, Medical Academy and Brodnowski Hospital, Warsaw, c Department of Gynecologic Oncology, Medical Academy, Poznan, Poland

AIM: To evaluate prognostic/predictive significance of TP53, MEK1, XIAP, BCL-2 and BAX proteins in ovarian carcinomas treated with platinum-based chemotherapy. MATERIAL AND METHODS: Immunohistochemical analysis was performed on 229 ovarian carcinomas FIGO stage IIB-IV. Multivariate analysis with Cox model was performed in the whole group, and in a TP53(-) and TP53(+) subgroup. RESULTS: Endometrioid and clear cell carcinomas were negatively associated with TP53 (p=0.001) and positively with BCL-2 (p=0.003) and MEK1 (p=0.049) expressions. TP53 (p=0.032) and BAX (p=0.018) positivity were associated with poor tumor differentiation. Loss of MEK1 expression was found with advancing FIGO stage (p=.002). In the whole group, overall survival (OS), disease-free survival (DFS) and complete remission (CR) were influenced by patient's age, FIGO stage, and residual tumor size (RT). OS in the TP53(-) group was associated with FIGO stage (p=.045), while in the TP53(+) group with patient's age (p=.002) and RT (p<.001). OS in the FIGO IIIC group was negatively associated with PAC chemotherapy (p=.04) in the TP53(-) group. CR in the TP53(-) group was associated with patient's age (p=.03), RT (p=.005), and BCL-2 positivity (p=.05), while in the TP53(+) group with RT only (p<.001). DFS in the TP53(-) group correlated with RT (p=.06), while in the TP53(+) group with FIGO stage (p=.01) and BAX positivity (p=.005). CONCLUSION: Our results suggest that binomial TP53 status divides ovarian carcinomas into two biologically distinct groups that differ in prognostic and predictive factors. Apparently, MEK1 and XIAP expressions do not influence outcome in ovarian cancer patients treated with platinum-based chemotherapy.

KEY WORDS: ovarian cancer, apoptosis proteins, response to chemotherapy.

For more information, contact jolantak@coi.waw.pl

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Prognostic Markers.

http://www.cancerprev.org/Journal/Issues/26/101/1294/4510