Chromosomal Instability, DNA Index, Dysplasia, and Subsite in Oral Premalignancy as Intermediate Endpoints of Risk of Cancer

Abstract

Chromosomal instability and aneuploidy may represent biomarkers of oral exposure to damaging agents and early signs of clinical disease according to the theory of "oral field cancerization." The hypothesis was tested that the DNA index (DI) values, obtained by high-resolution DNA flow cytometry (DNA-FCM), may potentially contribute to oral cancer risk prediction. For this purpose, the DI of oral fields of normal-appearing mucosa and oral potentially malignant disorders (OPMDs) in 165 consecutive patients was tested for association with dysplasia and/or the oral subsites of tongue and floor of the mouth taken as high-risk intermediate endpoints surrogate of cancer clinical endpoints. The association was evaluated by logistic regression using patient gender, age, tobacco, cigarette smoking habit, and alcohol abuse as confounding variables. Different DI models provided evidence of statistical significant associations. Subdividing the DI values in diploid, near-diploid aneuploid, and high or multiple aneuploid from both OPMDs and oral normal-appearing mucosa, ORs, respectively, of 1, 4.3 (P = 0.001), and 18.4 (P < 0.0005) were obtained. Routine DI analysis by high-resolution DNA-FCM seems potentially useful to complement dysplasia and subsite analysis for assessment of oral cancer risk prediction and for a better management of the patients with OPMDs. Work is in progress to validate the present findings in a prospective study with clinical endpoints. Identifying DNA abnormalities in oral premalignancy may lead to biomarkers of oral exposure and cancer risk and potentially to more effective prevention measures.