Evaluation of TGF-alpha and EGFR expression in oral leukoplakia and oral submucous fibrosis by quantitative immunohistochemistry

Objective: Oral leukoplakia (OL) and oral submucous fibrosis (OSMF) are cli nically distinct preneoplastic states that precede the development of oral squamous cell carcinoma. Recently, attempts are being made to identify spec ific molecular event(s) as prognostic markers to identify oral precancerous lesions with higher malignant potential. The goal of the present study was to evaluate the expression of EGFR and its ligand TGF-alpha in OL with dys plasia and OSMF as intermediate markers of malignancy by quantitative immun ohistochemistry. Methods: Oral tissues were stained with monoclonal antibod ies to TGF-alpha and EGFR. The results were analyzed with Photoquant image analysis software. Results: The expression of TGF-alpha and EGFR was upregu lated in OL, OSMF and oral squamous cell carcinomas relative to normal oral mucosa. The area and intensity of staining of TGF-alpha in the proliferati ve layers (stratum germinativum) increased linearly in OL with mild, modera te and severe dysplasia as compared to control mucosa (p < 0.05). EGFR leve ls increased linearly in the stratum spinosum in OL with increasing degrees of dysplasia (p < 0.05). In general, the expression of both proteins in OS MF was similar to that in OL with moderate dysplasia. Conclusions: EGFR and TGF-alpha represent early markers of malignancy in OL with dysplasia. Quan titative measurement of these proteins may provide intermediate endpoints i n prospective chemopreventive trials. Copyright (C) 2001 S. Karger AG, Base l.