Marcadores moleculares en pacientes con cáncer de cuello uterino tratadas con quimioterapia neoadyuvante y radioterapia

CUELLO CARRI¨®N, F.D.; VARGAS ROIG, L.M.; LO CASTRO, G.; LOTFI, H.; D´ANGELO, C.; JOFR¨¦, J.; FANELLI, M.A.; CIOCCA, D.R.

ONCOLOGÍA CLÍNICA

Alfa Beta

Lugar: Argentina; Año: 2001 vol. 6 p. 511 - 519

1669-6336

Objectives: The purpose of this prospective study was to assess the changes and the predictive value ofp53, p21WAFl/SDll/ClP1, hMLH1, hMSH2, Bcl-2, and TUNEL in locally advanced cervical cancer patients treated with induction chemotherapy and radiation therapy. Patients and methods: Cervical tissues were obtained from 24 patients (IB-bulky/IIIB, 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 express ion of the molecular markers. Apoptosis was evaluated with a recently improved TUNEL technique. Statistical analyses were performed to compare the changes in the molecular markers and to correlate them with the clinical outcome (median follow-up: 31 months for cisplatin-based group and 19 months for vinorelbine-ifosfamide treated patients). Results and conclusions: Induction chemotherapy did not enhance the possibility of survival of the patients, 50% presented progressive disease (PD) or death (D). p21WAFl/SDll/ClP1, hMSH2, 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 all patients with a low TUNEL index (¡Ü 1.5 mean value of pre- and post-chemotherapy paired biopsies) was significantly poorer than those who presented a higher TUNEL index (p< 0.009). Our results showed that induction chemotherapy (the two chemotherapy protocols applied in this study) did not improve the survival of cervical cancel´ patients. We also found that the express ion of all molecular markers was not consistently modified by chemotherapy, and that patients whose tumors showed positive p53, high PCNA, low TUNEL index showed poor survival.