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Annals of Oncology 14:1078-1085, 2003
© 2003 European Society for Medical Oncology

Original Paper

P21WAF1, P27KIP1, TP53 and C-MYC analysis in 204 ovarian carcinomas treated with platinum-based regimens

J. Plisiecka-Halasa1, G. Karpinska5, T. Szymanska1, I. Ziólkowska3, R. Madry4, A. Timorek6, J. Debniak7, M. Ulanska9, M. Jedryka10, A. Chudecka-Glaz11, M. Klimek12, A. Rembiszewska1, E. Kraszewska2, B. Dybowski1, J. Markowska4, J. Emerich7, A. Pluzanska9, M. Goluda10, I. Rzepka-Górska11, K. Urbanski12, J. Zielinski3, J. Stelmachów6, M. Chrabowska8 and J. Kupryjanczyk1,5,+

Departments of 1 Molecular Pathology, 2 Biostatistics, 3 Gynecologic Oncology, Institute of Oncology, Roentgena, Warsaw; 4 University of Medical Sciences, Poznan; Departments of 5 Pathology and 6 Obstetrics and Gynecology, Bródnowski Hospital and Second Faculty of Medicine, Medical University, Warsaw; 7 Second Gynecological Department, and 8 Department of Pathology, Medical University, Gdansk; 9 Department of Chemotherapy, Medical University, Lodz; 10 Second Department of Gynecology, Medical Academy, Wroclaw; 11 Department of Gynecological Surgery and Oncology of Adults and Adolescents, Pomeranian Academy of Medicine, Szczecin; 12 Department of Gynecologic Oncology, Institute of Oncology, Kraków, Poland

Received 21 November 2002; revised 24 March 2003; accepted 1 April 2003

Background:

The prognostic and predictive value of cell cycle regulatory proteins in ovarian cancer has not been established. We evaluated the clinical and biological significance of P21WAF1, P27KIP1, C-MYC, TP53 and Ki67 expressions in ovarian cancer patients.

Materials and methods:

Immunohistochemical analysis was performed on 204 ovarian carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IV treated with platinum-based chemotherapy. Multivariate analysis with Cox and logistic regression models was performed in the whole group, and in the TP53-negative and TP53-positive subgroups.

Results:

High P21WAF1 labeling index (LI) was an independent positive predictor of platinum-sensitive response (P = 0.02). Overall survival was positively influenced by P21WAF1 LI (P = 0.02) or by P21WAF1 plus P27KIP1 LI (P = 0.004) in the TP53-negative group only. Ki67 LI showed borderline association with disease-free survival (P = 0.05). Growth fraction was negatively associated with P21WAF1 and P27KIP1 indices in the TP53-negative group (P = 0.023 and 0.008, respectively), and these associations were borderline or lost in the TP53-positive group. Endometrioid and clear cell carcinomas differed from other carcinomas by having a low incidence of TP53 accumulation, a high incidence of C-MYC overexpression (70%) and a low median Ki67 LI (all with P <0.001).

Conclusions:

We have shown an independent predictive value of P21WAF1 LI in ovarian carcinoma patients. The prognostic value of P21WAF1 and P21WAF1 plus P27KIP1 LI was determined by TP53 status. A high frequency of C-MYC overexpression in endometrioid and clear cell carcinomas may suggest its role in the development of these tumor types.

Key words: Ki67, C-MYC, ovarian cancer, P27KIP1, P21WAF1, TP53


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