Predictive Factors in Patients with Cancer of the Uterine Cervix Treated with Induction Chemotherapy and Radiation Therapy

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

New Orleans, Louisiana, USA

Congreso; 92nd Annual Meeting of the American Association for Cancer Research; 2001

American Association for Cancer Research

The purpose of this prospective study was to assess the predictive value of p53, p21WAF1/SDII/CIP1, PCNA, hMLH1, hMSH2, BcI-2 and TUNEL in locally advanced cervical cancer patients treated with induction chemotherapy and radiation therapy. Cervical tissues were obtained Irom 24 patients (lBulky/IlIB, 95% with squamous cell carcinomas), before chemotherapy and about 30 days after chemotherapy. Cisplatin-based drugs were administered to 13 patients, since the outcome of these patients was poor, vinorelbine and ifosfamide was administered to the other 11 patients. After chemotherapy, all patients received radiotherapy. Immunohistochemistry was applied to detect in the paired biopsies the expression of the molecular markers. Apoptosis was evaluated with a recently improved TUNEL technique. Statistical analysis were performed to compare the changes in the molecular markers and to correlate then with the clinical outcome (median follow-up: 31 months for cisplatin-based group and 19 months for vinorelbine-ifosfamide treated patients). Induction chemotherapies did not enhance the survival of the patients, 50% presented progressive disease (PD) or death (D). p21 WAF1/SDII/CIP1, hMLH1, hMSH2, and Bcl-2 did not show significant changes after chemotherapy, the expression levels of these markers did not correlate with patient follow-up. p53 expression did not change after chemotherapy, patients with p53-positive tumors showed a tendency to have poor survival. Increased PCNA levels after chemotherapy were more frequently found in patients suffering PD or D than those who presented disease-free or stable disease (50% versus 17% respectively, p<0.04). Survival of patients with a low TUNEL index (=/<1.5 mean value of pre- and post-chemoterapy paired biopsies) was significantly poorer than those who presented a higher TUNEL index (p<0.009). Patients whose tumors showed a combination of positive p53, high PCNA and low TUNEL showed the poorest survival. In conclusion, we have identified useful predictive molecular markers in cervical cancer patients treated with induction chemotherapy and radiation therapy. Supported by CONICET and ANPCyT of Argentina.(50% versus 17% respectively, p<0.04). Survival of patients with a low TUNEL index (=/<1.5 mean value of pre- and post-chemoterapy paired biopsies) was significantly poorer than those who presented a higher TUNEL index (p<0.009). Patients whose tumors showed a combination of positive p53, high PCNA and low TUNEL showed the poorest survival. In conclusion, we have identified useful predictive molecular markers in cervical cancer patients treated with induction chemotherapy and radiation therapy. Supported by CONICET and ANPCyT of Argentina.