Loss of Heterozygosity on Chromosome 6p21.2 as a Potential Marker for Recurrence after Radiotherapy of Human Cervical Cancer

• Published in: Clinical cancer research 2000-03, Vol.6 (3), p.1079-1085
• Main Authors: Harima, Y, Harima, K, Sawada, S, Tanaka, Y, Arita, S, Ohnishi, T
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Chromosomes, Human, Pair 6 - genetics; DNA Mutational Analysis; DNA, Neoplasm - chemistry; DNA, Neoplasm - genetics; Female; Genetic Markers; Humans; Loss of Heterozygosity; Middle Aged; Mutation; Neoplasm Recurrence, Local; Neoplasm Staging; Papillomaviridae; Papillomavirus Infections; Polymorphism, Single-Stranded Conformational; Survival Analysis; Tumor Suppressor Protein p53 - genetics; Tumor Virus Infections; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - radiotherapy
• ISSN: 1078-0432; 1557-3265

Cervical carcinomas develop as a result of multiple genetic alterations, and specific alterations lead to specific clinical behavior. However, the effect of such alterations on the recurrence of cervical cancer after radiotherapy remains unknown. Chromosome arm 6p is one of those most frequently involved in a loss of heterozygosity (LOH) in patients with cervical carcinoma. The aim of this study was to identify the correlation between the LOH on chromosome 6p21.2 and the recurrence of cervical cancer after radiotherapy. A total of 62 patients with cervical cancer (stage I, 4 patients; stage II, 9 patients; stage III, 37 patients; and stage IV, 12 patients) were included in this study. All patients were treated with definitive radiotherapy. We analyzed specimens from the tumors and venous blood of all patients. Tumors and normal DNA were analyzed by PCR for genetic losses at three polymorphic microsatellite loci ( D6S276, D6S1624, and D6S1583 ). Chromosome 6p21.2 is involved in the LOH in 46.8% (29 of 62) of the informative carcinomas. Ten patients had a local recurrence, 4 had distant metastases, and 13 had both local recurrence and distant metastases after radiotherapy. To evaluate the relationship between the recurrence after radiotherapy and LOH on chromosome 6p21.2, we divided the patients into those with cancer recurrence ( n = 27) and those without recurrence ( n = 35). LOH on chromosome 6p21.2 was correlated with recurrence after radiotherapy ( P = 0.006). The tumors in patients with recurrence were significantly larger than those in patients without recurrence ( P = 0.003). However, there was no correlation between the sizes and stages of tumors and the LOH on chromosome 6p21.2. In addition, both overall survival and relapse-free survival were significantly worse for the patients with LOH as compared with those without LOH ( P = 0.02 and P = 0.002, respectively). The results of this study suggest that LOH on 6p21.2 is correlated with recurrence of cervical carcinoma after radiotherapy.