IMMUNOHISTOCHEMICAL EXPRESSION OF EZH2 IN ATYPICAL PAPILLARY EPITHELIAL PROLIFERATIONS OF THE ORAL CAVITY: A POTENTIAL MARKER FOR MALIGNANT TRANSFORMATION

Background Enhancer of zeste homolog-2 (EZH2) is a member of the polycomb group PcG of proteins; the genes that are involved in transcriptional repression. Cell cycle regulation and cell proliferation is associated with EZH2 expression and EZH2 overexpression stimulates cell proliferation and invasiveness. Conversely, inhibition of EZH2 precludes cancer cell invasiveness through inhibition of cell proliferation. Atypical papillary epithelial proliferation (AEP) is a histologic diagnosis rendered for oral lesions with confounding microscopic features, neither overtly benign nor unequivocally malignant. Aim To evaluate EZH2 antibody expression through immunohistochemical testing to delineate the potential of malignant transformation in AEP by comparing and contrasting with unequivocally benign papillary lesions represented by inflammatory papillary hyperplasia (IPH) and malignant papillary lesions represented by papillary well differentiated squamous cell carcinoma (PSCC). Materials and Methods 10 cases each of AEP, IPH and PSCC were retrieved from the University of Florida, Oral Pathology Biopsy Service archive and stained with Anti-KMT6/EZH2 antibody. The cases were reviewed and the extent and pattern of EZH2 expression were assessed. The results were analyzed for statistical significance using Fischer's exact test. Results The pattern and intensity of EZH2 expression in AEP and PSCC demonstrated statistically significant differences when compared to IPH (p=0.002). In addition, the basal cell layer showed EZH2 expression in all the cases of AEP (100%) and PSCC (100%) but only 3 out of 10 (30%) in IPH (p=0.000), comparable to normal oral epithelial control tissue. Conclusion EZH2 expression in AEP is more similar to malignant processes than benign lesions. The pattern of basal cell layer expression of EZH2 could be a potential prognostic indicator of malignant transformation risk in oral AEP lesions. A subsequent study by our group to assess EZH2 expression with respect to clinical outcome in AEP lesions is ongoing.