MICROSATELLITE ALTERATION AT CHROMOSOME 3P LOCI IN NEUROENDOCRINE ANDNON-NEUROENDOCRINE LUNG-TUMORS - HISTOGENETIC AND CLINICAL RELEVANCE

Although chromosome 3p regions are the most frequent site for genetic alterations in small-cell lung carcinoma (SCLC) and non-small-cell lun g carcinoma (NSCLC), the extent of such abnormality in carcinoid tumor s remained to be investigated. Moreover, the histogenetic and biologic al implications of these findings in non-carcinoid lung tumors remain unclear. We studied eight microsatellite loci on chromosome 3p regions by multiplex polymerase chain reaction in paired normal and tumor DNA from 17 carcinoid tumors, 5 SCLCs, and 38 NSCLCs to determine the his togenetic and the clinical significance of their alterations in these neoplasms. Our results revealed a lack, of microsatellite abnormalitie s at all loci tested in both typical and atypical carcinoid tumors. SC LCs and NSCLCs showed loss of heterozygosity ia 100% (5/5) and 58.0% ( 22/38), respectively. Loss of heterozygosity at more than two loci cor related significantly with poor histological differentiation and were preponderantly found in high proliferative index and DNA aneuploid NSC LCs. Microsatellite instability was noted in only one (1.7%) of the le sions. Our study suggests that 1) the difference in chromosome 3p, alt erations between carcinoid tumors and SCLCs favors a stochastic rather than linear evolution of these tumors, 2) 3p alterations may constitu te an initial event in the development of small cell carcinomas, and 3 ) loss of heterozygosity at 3p loci is associated with aggressive tumo r characteristics in non-small-cell carcinomas.