Genetic alterations on chromosome 17p associated with response to radiotherapy in bulky cervical cancer

Chromosome 17 alterations are found in more cancers than those of any other chromosome, and frequently involve the p53 gene on 17p13. The aim of this study was to identify the correlations between the presence of loss of hete rozygosity (LOH) and microsatellite instability (MI) on chromosome 17p13 in patients with cervical cancer and the patients' response to radiotherapy. A total of 50 patients were treated with definitive radiotherapy. We perfor med biopsies and took specimens from the tumour and venous blood of all pat ients. Tumour and normal DNAs were analysed by polymerase chain reaction fo r genetic losses and instability at three polymorphic microsatellite loci m apped to 17p13. Nineteen of the 50 tumours (38%) displayed a genetic altera tion (GA) on 17p13, 16 (32%) were found to have LOH, and three (6%) showed MI. The sizes of the tumours of the GA-positive patients were significantly greater than those of the GA-negative patients (P = 0.009). The mean tumou r diameter of all patients was 6 +/- 2.4 cm. We divided the patients into t hose with tumours smaller than 6 cm in diameter (n = 26) and those with tum ours equal to or greater than 6 cm in diameter (n = 24). The former group s urvived significantly longer compared to the latter group (P = 0.0002). Amo ng the patients with < 6 cm tumours, all six GA-positive patients are alive with no evidence of disease (NED), whereas of the 20 GA-negative patients, 18 have NED and two are alive with disease (AWD) or suffered cancer-caused death (CD), Thus, there was no correlation between GA and radiotherapy res ponse in the tumours smaller than 6 cm. However, among the patients with < 6 cm tumours, two of the GA-positive patients have NED and 11 are AWD/CD, w hereas seven of the GA-negative patients have NED and four are AWD/CD, Amon g the patients with < 6 cm tumours, the response to radiotherapy of the GA- positive patients were significantly poorer than those of the GA-negative p atients (P = 0.02). In addition, the GA-negative patients survived signific antly longer compared to the GA-positive patients (P = 0.026), The results of this study suggest that GA increases with tumour growth. Improved succes s in the management of bulky cervical cancer requires a better understandin g of its biological behaviour.