LOSS OF HETEROZYGOSITY AT 5Q21-22 (ADENOMATOUS POLYPOSIS-COLI GENE REGION) IN ORAL SQUAMOUS-CELL CARCINOMA IS COMMON AND CORRELATED WITH ADVANCED DISEASE

We determined the frequency of loss of heterozygosity (LOH) at chromos ome 5q21-22 (adenomatous polyposis gene region) in oral SCC from 49 pa tients using PCR-based assays. Of 43 informative (heterozygous) tumors , 41.9% [95% confidence interval(CI) = 27.0, 57.9] contained LOH at 5q 21-22. LOH at 5q21-22 was strongly associated with stage at diagnosis: 100% (3/3), 50% (13/26), and 14% (2/14) of tumors from patients with distant metastases, regional spread, and localized disease, respective ly, contained this genetic alteration (P = 0.01). There were no statis tically significant associations between LOH at 5q21-22 and other pati ent or tumor characteristics, but LOH was more commonly found in the t umors of heavy smokers, infrequent alcohol consumers, and in tumors co ntaining either p53 mutations or HPV-DNA. In univariate analyses, LOH at 5q21-22 was associated with poor prognosis (hazard ratio = 1.8, 95% CI 0.8, 4.5); this relationship did not persist after adjustment for stage of disease (hazard ratio = 1.1, 95% CI = 0.4, 3.1). These data p rovide further evidence that inactivation of the APC gene and/or other genes at 5q21-22 is common and may be involved in the development and /or progression of oral SCC. Larger studies are needed to determine wh ether LOH at 5q21-22 is linked to known oral SCC etiologic factors and /or the prognosis of oral SCC patients, as well as to genetic instabil ity at other loci involved in these malignancies.