Increased expression of c-erbB-3 protein and proliferating cell nuclear antigen during development of verrucous carcinoma of the oral mucosa

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Abstract
BACKGROUND The roles of c‐erbB‐3 gene and protein in the pathogenesis, progression, and outcome of oral carcinoma remain unknown. To determine whether c‐erbB‐3 expression could serve as an indicator of progression from premalignant to malignant transformation and of prognoses in patients with oral carcinoma, the authors examined the relation between the expression of c‐erbB‐3 protein and cell proliferation activity during the development of oral verrucous carcinoma (VC). METHODS Immunohistochemical techniques were used to evaluate c‐erbB‐3 protein and proliferative cell nuclear antigen (PCNA). Sixty‐one samples (36 patients) of verrucous hyperplasia (VH), VC, and well differentiated squamous cell carcinoma arising from verrucous carcinoma (V‐WSCC) in the oral mucosa were examined. RESULTS Normal human oral mucosa showed weak c‐erbB‐3 immunostaining, predominantly on the epithelial surface. In contrast, 7 (39%) of 18 VHs, 25 (84%) of 31 VCs, and all (100%) of 12 V‐WSCCs demonstrated overexpression of c‐erbB‐3 protein with increased expression of PCNA in some premalignant epithelial cells and many tumor cells. This finding suggested the involvement of c‐erbB‐3 gene in the progression from VH to VC and V‐WSCC. CONCLUSIONS Overexpression of c‐erbB‐3 protein correlated with increased PCNA labeling index, indicating that c‐erbB‐3 may contribute to malignant transformation and tumor growth. Further, patients with high expression of both c‐erbB‐3 and PCNA had a poor outcome. Study results suggested that c‐erbB‐3 expression was an index of malignancy during progression from VH to VC and V‐WSCC and might have been involved in the outcome of oral carcinoma patients. Cancer 2000;89:2597–605. © 2000 American Cancer Society.