Apoptosis and Cell Proliferation Are Useful Prognostic Factors in Patients with Cervical Carcinomas

CUELLO-CARRIÓN, F.D.; VARGAS ROIG, L.M.; FANELLI, M.A.; CIOCCA, D.R.

New Orleans, Louisiana, USA

Congreso; 36th Annual Meeting of the American Society for Clinical Oncology; 2000

American Society for Clinical Oncology

The main objective of administering chemotherapies to cancer patients is to increase cell death and/or to decrease cell proliferation. In this study we have investigated these two parameters in paired pre- and postchemotherapy biopsy samples (formalin-fixed, paraffin sections) from patients with locally advanced cervical cancer receiving neoadjuvant chemotherapy. All patients received radiotherapy after induction chemotherapy. The study involved 24 patients, 13 patients received cisplatin-based chemotherapy and 11 patients were treated with vinorelbine/ifosfamide. Apoptosis was detected with a modified in situ TUNEL technique that improved the detection of apoptotic cells (recently reported by us, J. Histochem. Cytochem. 47:837,1999). Immunohistochemistry was performed with specific antibodies to detect Ki-67, p53, hMLH1, hMSH2, and p21 (WAF1/Cip1) proteins. The mismatch repair proteins hMLH1 and hMSH2, and the cell cycle control protein p21 were not modified by chemotherapy, moreover expression of these proteins did not correlate with the outcome of the disease. Patients with poor clinical outcome (progressive disease/death, median follow-up = 24 months) showed mutated/inactive p53 in 40% of the cases and a decrease in the cell cycle in 70% of the cases. In the post-chemotherapy biopsies, all patients with poor clinical outcome (n = 9) showed low apoptosis, no increase in the apoptotic index, or even a decrease in the apoptotic index. These results suggest that evaluation of apoptosis and cell proliferation is useful in predicting the clinical outcome in patients with locally advanced cervical cancer treated with induction chemotherapy followed by radiotherapy. Study supported by grants from National Agency for Promotion of Science and Technology, and National University of Cuyo, Argentina.