SEQUENTIAL LOSS OF HETEROZYGOSITY AT MICROSATELLITE MOTIFS IN PREINVASIVE AND INVASIVE HEAD AND NECK SQUAMOUS CARCINOMA

Studies of sequential molecular alterations in noninvasive and invasiv e head and neck squamous carcinoma are few in number. Consequently, th e genetic changes associated with the neoplastic transformation of the se carcinomas have not been defined. To identify chromosomal alteratio ns in preinvasive and invasive head and neck squamous carcinoma, we an alyzed DNA from microdissected normal squamous epithelium, severe dysp lasia, and invasive carcinoma samples from 20 patients for Loss of het erozygosity (LOH) at microsatellite loci by multiplex PCR. Twenty-five microsatellite repeats on chromosomes 3p, 5q, 8p, 9p and 90, 11q, 17p , 17q, and 18p and 18q regions were used. In informative cases, LOH in noninvasive lesions was observed in 9p (28%), 9q and 18q (10 %), 11q and 17p (7%), and 3p and 18p (5%). A high incidence of LOH in invasive carcinoma was observed at 9p (72%), 8p (53%), 3p (47%), 9q (35%), and 11q (33%). LOH was also associated with DNA aneuploidy, high tumor st age, and poor histological differentiation. Our results indicate that: (a) the high incidence of LOH at loci on chromosomes 9p, gp, 3p, 9q, and 11q implicate these regions in head and neck squamous carcinoma tu morigenesis; (b) 9p loci alterations are manifested in the early devel opment of these tumors; (c) LOH is correlated with poor prognostic cli nicopathological factors; and (d) LOH at 8p loci appears to be associa ted with the tumor's aggressive features.