MICROSATELLITE INSTABILITY IN PREINVASIVE AND INVASIVE HEAD AND NECK SQUAMOUS CARCINOMA

To investigate the extent and significance of microsatellite instabili ty in head and neck carcinogenesis we analyzed DNA extracted from norm al squamous epithelium, severe dysplasia, and corresponding carcinoma specimens from 20 patients by multiplex polymerase chain reaction. Loc i on chromosomes 3p, 5p, 5q, 8p, 9p, 9q, 11q, 17p, 17q, 18P, and 18q w ere selected for analysis. Our results show that three of the dysplasi as (15.0%) and six of the invasive carcinomas (30.0%) manifested insta bility at multiple loci. Two of the dysplastic lesions had identical a lterations in the corresponding carcinomas and one showed instability differences ire only two of eight loci, Normal squamous epitheleum lac ked microsatellite instability. No apparent association between smokin g, alcohol use, or family history of cancer and instability was found in this small cohort, Invasive carcinomas with instability were relati vely more poorly differentiated and had a higher stage and a high prol iferative fraction. Our study indicates that microsatellite instabilit y is 1) noted in a small subset of dysplastic lesions of head and neck squamous epithelium and 2) present in approximately one-third of inva sive lesions, usually with aggressive characteristics, and may clinica lly be a late event associated with tumor progression.