ALLELIC IMBALANCE AT CHROMOSOMAL LOCI IMPLICATED IN THE PATHOGENESIS OF ORAL PRECANCER, CUMULATIVE LOSS AND ITS RELATIONSHIP WITH PROGRESSION TO CANCER

A microsatellite assay was used to screen 31 potentially malignant ora l lesions presenting as leukoplakia and erythroplakia, with histologic al evidence of dysplasia, for genetic abnormalities at loci which freq uently show allelic imbalance when oral squamous cell carcinomas (SCC) are examined. The microsatellite and restriction fragment length poly morphism (RFLP) markers selected were at 3p21, 8p21-23, 9p21 and inclu ded sequences within the Rb (13q14.2), p53 (17p13.1) and DCC (18q21.1) tumour suppressor genes. 8 patients subsequently developed an invasiv e tumour at the same site, or within 2 cm of the premalignant lesion. A further 8 patients developed SCC at a distant site. Seventy-seven pe r cent (24/31) of these potentially malignant lesions showed allelic i mbalance (AI) and 55% (17/31) of cases showed microsatellite instabili ty (msi). The probability of developing SCC was much greater for patie nts with lesions showing Al at two or more relevant loci (P=0.008 by t he logrank test) than the group with At at fewer loci. The estimated p robability of development of SCC in this group by 5 years was 73% (95% Cl:50-92%). This suggests that determining the number of genetic abnor malities in a potentially malignant lesion can help identify patients with true precancers who should be followed closely to ensure that the y receive chemoprevention and appropriate advice to limit risk factors , and to allow the early detection of invasive lesions. (C) 1998 Elsev ier Science Ltd. All rights reserved.