FOXP3 lymphocyte status may predict the risk of malignant transformation in oral leukoplakia

Abstract Objectives Oral leukoplakia (OL) is a sign of potentially malignant disorders of the oral mucosa. The risk of malignant transformation of OL is challenging to assess. Furthermore, predictive biomarkers of malignant transformation have not been fully established. We examined the transcriptional status of factor forkhead box P3+ (FOXP3+) lymphocytes, which confer an immune-suppressive microenvironment, in OL and its potential value as a predictor for OL malignant transformation in two independent cohorts of patients. Methods A total of 165 patients who had been histopathologically diagnosed with OL were enrolled in this retrospective study. Patients were divided into derivation and validation cohorts. Cutoff values for the number of FOXP3+ lymphocytes (≥15) were determined using receiver operator characteristic analyses. Results In the derivation cohort, among FOXP3-high OL patients, FOXP3+ lymphocyte status was the only factor associated with malignant transformation in both univariate and multivariate analyses. There was a similar trend in the validation cohort. Moreover, FOXP3+ lymphocyte expression status was correlated with dysplasia grade. Conclusions These results suggest that FOXP3+ lymphocyte status is a potential predictive biomarker in patients with OL and may affect multistep carcinogenesis from OL to oral squamous cell carcinoma.