50 O - Loss of heterozygosity (LOH) AT 5q21 and prognosis in resected non-small cell lung cancer (NSCLC)

Abstract

Chromosome 5 appears to be an important target in the pathogenesis of neoplasms including NSCLC. These abnormalities include frequent LOH at 5q21 which contains the APC and MCC genes. We analyzed the frequency and clinical relevance of LOH at the APC/MCC loci in 60 cases of resected NSCLC. Tumor and normal DNA were amplified by PCR at two microsatellite markers: D5S82 (APC gene) and MCC (within MCC gene). Polymorphic PCR products were resolved by electrophoresis through 6% denaturing polyacrylamide gels. Forty-one of the 60 stage I-IIIA NSCLC were informative (heterozygous for LOH analysis at the APC and/or MCC loci). LOH at the APC/MCC loci was found in 20% (8 of 41). No significant differences of LOH were observed among histological types (15% in squamous cell carcinoma and 36% in adenocarcinoma). LOH at 5q was higher in stage IIIA (40%) than in earlier stages (16%) and a trend towards worse survival was detected in stage IIIA patients with LOH at 5q (9 months median survival time) in comparison with patients without LOH (21 months). In addition, LOH was not found to be linked to a higher frequency of mutations affecting K-ras and p53 genes. Our findings underline that LOH at 5q21 plays a role in NSCLC progression and could help to identify resected NSCLC patients with poor prognosis.