Loss of heterozygosity (LOH) is one of the most important mechanisms for inactivation of tumor-suppressor genes. Studies of LOH in patients with cervical carcinoma have reported a high frequency of LOH on 3p21.3, 6p21.2, 17p13.1, and 18q21.2. Our study explored whether p53 status, human papilloma virus (HPV), and LOH on chromosome 3p21.3, 6p21.2, 17p13.1, and 18q21.2 are associated with treatment outcome in 65 patients with cervical cancer after radiotherapy. Tumors and normal DNA were analyzed by polymerase chain reaction (PCR) for genetic losses at 10 polymorphic microsatellite loci. The presence of HPV and its type were analyzed by PCR-based assay using the consensus primers for E6, E7, and L1 region. Mutations of the p53 gene were identified by a single-strand conformation polymorphism analysis. Chromosomes 3p21.3, 6p21.2, 17p13.1, and 18q21.2 were involved in the LOH in 23.1%, 41.5%%, 33.8%, and 23.1% of the tumors in our study, respectively. HPV-positive tumors were found in 73.8% of the patients and p53 mutation in 10.8%. The patients with LOH on chromosome 6p21.2 and 18q21.2 survived significantly shorter compared with those without LOH on chromosome 6p21.2 and 18q21.2 in both the overall survival (P = 0.006 and P = 0.007) and the disease-free survival (P = 0.005 and P = 0.008). The HPV-negative patients survived significantly shorter compared with the HPV-positive patients in both the overall survival (P = 0.01) and the disease-free survival (P = 0.04). According to multivariate analysis, HPV status (P = 0.0004, P = 0.01), LOH on 6p21.2 (P = 0.006, P = 0.02), and LOH on 18q21.2 (in both P = 0.01) is a significant predictor of both overall and disease-free survival time. The results of our study suggest that absence of HPV infection, LOH on 6p21.2, and LOH on 18q21.2 are the most important determinants of outcome of patients with cervical carcinoma after radiotherapy.
Copyright 2001 Wiley-Liss, Inc.