Gross genomic aberrations in precancers: clinical implications of a long-term follow-up study in oral erythroplakias.

Abstract

Gross genomic aberrations are increasingly seen as a cause rather than a consequence of carcinogenesis. Carcinomas may be prevented by systemically acting agents when used in high-risk individuals. If gross genomic aberrations could be shown to be predictive markers in precancers, they could serve as a tool for identifying high-risk individuals to be included in chemopreventive trials. To investigate the predictive power of gross genomic aberrations in several types of oral premalignancies, we analyzed 57 biopsies from oral erythroplakias of 37 patients, both histologically and for DNA content. DNA content was measured by high-resolution image cytometry, and distribution histograms of DNA content were generated and interpreted according to established protocols. The primary end point was cancer-free survival. Fifty-seven dysplastic oral red lesions from 37 patients were investigated. Forty-one lesions from 25 patients were classified with aberrant DNA content (DNA aneuploidy), of which 23 patients (92%) later developed an oral carcinoma (after a median observation time of 53 months; range, 29 to 79 months). Of 12 patients having altogether 16 lesions with normal DNA content, none developed a carcinoma (median observation time, 98 months; range, 23 to 163 months; P <.001). In multivariate analysis, DNA content was a significant prognostic factor (P <.001), whereas histologic grade, sex, use of tobacco, size and location of lesions, and the presence multiple of lesions were not. Gross genomic aberrations are highly predictive for the subsequent occurrence of carcinomas from a wide range of oral premalignancies.