CLINICAL CORRELATIONS WITH ALLELOTYPE IN SUPRAGLOTTIC SQUAMOUS CANCER

Frequent allelic loss at a genetically polymorphic locus in tumors is an established marker for the presence of a tumor suppressor gene in t he neighboring chromosomal region. This technique can be used to ident ify novel tumor suppressor genes and to monitor their status before th e cloning of the gene itself. We have used the polymerase chain reacti on and microsatellite loci on all 39 nonacrocentric autosomal chromoso mal arms to identify sites of frequent allelic loss in squamous cell c arcinomas of the supraglottic larynx. Our allelo-type identified seven chromosomal arms (3p, 5q, 8p, 9p, 9q, 13q, and 17p) likely to contain tumor suppressor genes frequently inactivated during squamous tumorig enesis in the larynx. We tested for associations between allelic losse s on these chromosomal arms and the clinical and histopathologic featu res of these tumors. Them were no correlations with either T or N clas sifications. Allelic loss on chromosomal arm 13q is significantly asso ciated with a number of histopathologic features characteristic of poo rly differentiated or histologically aggressive tumors. Allelic loss o n this arm also exhibits statistical trends toward association with ea rly tumor recurrence and poor survival. The association with survival was substantiated by a multivariate Cox proportional hazards model.