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Prognostic Significance of Allelic Imbalances on Chromosome 9p in Stage I Non-Small Cell Lung Carcinoma¹

Biology Division [Y. T., J. A., T. K., K. H., J. Y.], Pathology Division [M. N., Y. M., S. H.], and Cancer Information and Epidemiology Division [N. Y.], National Cancer Center Research Institute, Tokyo 104-0045, Japan, and First Department of Internal Medicine, Gunma University, School of Medicine, Gunma 371-8511, Japan [Y. T., R. S.]

Loss of heterozygosity (LOH) on chromosomes 2q, 9p, 18q, and 22q frequently occurs in advanced non-small cell lung carcinoma (NSCLC). The association of p53 mutations with prognosis is still unclear in NSCLC. Therefore, we investigated the prognostic significance of allelic imbalances (AI) on these chromosomes and p53 mutations in 108 cases of stage I NSCLC by PCR amplification of polymorphic dinucleotide repeat-containing sequences and PCR-single strand conformation polymorphism analysis. AI on 2q, 9p, 18q, and 22q was detected in 22, 38, 29, and 15% of cases, respectively, whereas p53 was mutated in 41% of stage I NSCLC. AI on 9p and 22q and p53 mutations were significantly associated with shortened survival of the patients (P = 0.010, 0.024, and 0.022, respectively). Although gender and smoking history showed more significant associations with prognosis than other clinicopathological and molecular parameters, independent prognostic significance for AI on 9p was observed (P = 0.002) in male patients with a positive smoking history. These results indicate that clinical aggressiveness of early-stage NSCLC can be partly defined by the presence of AI on chromosome 9p in cancer cells, and that AI on 9p could be a clinically useful prognostic indicator for early-stage NSCLC patients.

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