OBJECTIVE: Oral leukoplakia (OL) and oral submucous fibrosis (OSMF) are clinically distinct preneoplastic states that precede the development of oral squamous cell carcinoma. Recently, attempts are being made to identify specific 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 dysplasia and OSMF as intermediate markers of malignancy by quantitative immunohistochemistry. METHODS: Oral tissues were stained with monoclonal antibodies to TGF-alpha and EGFR. The results were analyzed with Photoquant image analysis software. RESULTS: The expression of TGF-alpha and EGFR was upregulated in OL, OSMF and oral squamous cell carcinomas relative to normal oral mucosa. The area and intensity of staining of TGF-alpha in the proliferative layers (stratum germinativum) increased linearly in OL with mild, moderate and severe dysplasia as compared to control mucosa (p < 0.05). EGFR levels increased linearly in the stratum spinosum in OL with increasing degrees of dysplasia (p < 0.05). In general, the expression of both proteins in OSMF was similar to that in OL with moderate dysplasia. CONCLUSIONS: EGFR and TGF-alpha represent early markers of malignancy in OL with dysplasia. Quantitative measurement of these proteins may provide intermediate endpoints in prospective chemopreventive trials. Copyright 2001 S. Karger AG, Basel
OBJECTIVE:Oral leukoplakia (OL) and oral submucous fibrosis (OSMF) are clinically distinct preneoplastic states that precede the development of oral squamous cell carcinoma. Recently, attempts are being made to identify specific 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 dysplasia and OSMF as intermediate markers of malignancy by quantitative immunohistochemistry. METHODS: Oral tissues were stained with monoclonal antibodies to TGF-alpha and EGFR. The results were analyzed with Photoquant image analysis software. RESULTS: The expression of TGF-alpha and EGFR was upregulated in OL, OSMF and oral squamous cell carcinomas relative to normal oral mucosa. The area and intensity of staining of TGF-alpha in the proliferative layers (stratum germinativum) increased linearly in OL with mild, moderate and severe dysplasia as compared to control mucosa (p < 0.05). EGFR levels increased linearly in the stratum spinosum in OL with increasing degrees of dysplasia (p < 0.05). In general, the expression of both proteins in OSMF was similar to that in OL with moderate dysplasia. CONCLUSIONS:EGFR and TGF-alpha represent early markers of malignancy in OL with dysplasia. Quantitative measurement of these proteins may provide intermediate endpoints in prospective chemopreventive trials. Copyright 2001 S. Karger AG, Basel