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

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.