Genetic alteration associated with response to radiotherapy in advanced cervical cancer

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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 heterozygosity (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 performed biopsies and took specimens from the tumour and venous blood of all patients. Tumour and normal DNAs were analyzed by polyrnerase chain reaction for genetic losses and instability at three polymorphic microsatellite locimapped to 17p13. Nineteen of theSO tumours (38%) displayed a genetic alteration (GA) on 17p13, sixteen (32%) were found to have LOH, and 3(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 tumour diameter of all patients wa … More s 6 * 2.4 cm. We divided the patients into those with tumours smaller than 6cm in diameter (n=26) and those with tumours equal to or greater than 6 cm in diameter (n=24). The former group survived significantly longer compared to the latter group(P=0.0002). Among the patients with < 6cm tumours, all 6 GA-positive patients are alive with no evidence of disease (NED), whereas of the 20 GA-negative patients, 18 have NED, and 2 are alive with disease (AWD) or suffered cancer-caused death (CD). Thus, there was no correlation between GA and radiotherapy response in the tumours smaller than 6 cm. However, among the patients with *6 cm turnours, 2 of the GA-positive patients have NED, and 11 are AWD/CD, whereas 7 of the GA-negative patients have NED, and 4 are AWD/CD.Among the patients with * 6 cm tumours, the response to radiotherapy of the GA-positive patients were significantly poorer than those of the GA-negative patients (P=0.02). In addition, the GA-negative patients survived significantly longer compared to the GA-positive patients (P=0.026). The results of this study suggest that GA increases with tumour growth. Improved success in the management of bulky cervical cancer requires a better understanding of its biological behavior. Less