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

Background: 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." Methods: 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. Results: 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 normalappearing mucosa, ORs, respectively, of 1, 4.3 (P = 0.001), and 18.4 (P < 0.0005) were obtained. Conclusion: 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. Impact: Identifying DNA abnormalities in oral premalignancy may lead to biomarkers of oral exposure and cancer risk and potentially to more effective prevention measures.