Impact of localized treatment in reducing risk of progression of low-gradeoral dysplasia: molecular evidence of incomplete resection

Currently, there is no consensus on the appropriate treatment for low-grade oral dysplasia. This is mainly due to the difficulty in predicting outcome for this heterogeneous group of lesions. In this study, we constructed a d etailed clinical history of 66 mild and moderate dysplasias in order to det ermine how treatment affected outcome, and to evaluate the effect of treatm ent on lesions with different genetic profiles, which are defined by patter ns of loss of heterozygosity (LOH) associated with low, intermediate and hi gh risk of progression [Clin. Cancer Res., 6, 357-62, 2000]. The results sh owed that although treatment guided by clinical removal of leukoplakia redu ced cancer progression risk in all three risk groups, the amount of reducti on in our study group did not reach statistical significance. To assess whe ther completeness of lesion removal was a major factor in recurrence, repea t biopsies at the primary sites were analyzed for persistent LOH status on chromosomes 3p, 4q, 8p, 9p, 11q, 13q and 17p. Strikingly, eight of 17 cases judged clinically removed contained the same molecular clones in the initi al and subsequent biopsies, suggesting incomplete removal. When molecular i nformation was included in the assessment of lesion removal, treatment sign ificantly reduced the risk of progression for cases with intermediate (P=0. 043) and thigh risk (P=0.001) genetic profiles, but not cases with low-risk profiles. A 9.1-fold decrease in progression risk was observed for chose w ith high-risk profile. Altogether, these data suggest the use of molecular profiles to guide the treatment of low-grade dysplasia. Our data also sugge st that currently an inadequate margin may in part be responsible for the h igh rate of recurrence, especially in high-risk lesions. (C) 2001 Elsevier Science Ltd. All rights reserved.