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.
Sakurai
K
K
Department of Oral and Maxillofacial Surgery, Hyogo College of Medicine, Nishinomiya, Japan. k-sakura@hyo-med.ac.jp
Urade
M
M
Takahashi
Y
Y
Kishimoto
H
H
Noguchi
K
K
Yasoshima
H
H
Kubota
A
A
D018289:Carcinoma, Verrucous / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D009061:Mouth Mucosa / Q000737:chemistry / Q000473:pathology; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000737:chemistry / Q000473:pathology; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis*; D020893:Receptor, ErbB-3 / Q000096:biosynthesis*
D018809:Proliferating Cell Nuclear Antigen; D020893:Receptor, ErbB-3