Co-localization of multiple ErbB receptors in stratified epithelium of oral squamous cell carcinoma

The expression of all four ErbB receptors was compared by immunohistochemis try, using receptor-specific polyclonal antisera, in 32 invasive, 11 in sit u carcinomas, six benign lesions, and 22 samples of histologically normal m ucosa adjacent to specimens of carcinoma originating from oral cavity epith elium. Among invasive and in situ carcinoma, EGFR expression was the most p revalent (in 29/32 and 8/11 cases, respectively) followed by ErbB2 (17/32 a nd 2/11) and ErbB4 (9/32 and 1/10), while ErbB3 was only detected in invasi ve tumours (12/32). Specific patterns included invasive tumours with expres sion of EGFR (8/32) or ErbB4 (1/32) alone, as well as different receptor co mbinations (EGFR + ErbB2, EGFR + ErbB4, EGFR + ErbB2 + ErbB3, EGFR + ErbB2 + ErbB4, and all four receptors). Simultaneous expression of three or four ErbB receptors correlated with tumour invasion (p = 2.2 x 10(-4)) and local ized in the intermediate epithelial cell layer of well and moderately diffe rentiated tumours. No other significant correlation with clinico-pathologic al features was noticed. Some benign lesions and histologically normal muco sa adjacent to carcinomas showed weak immunostaining of EGFR (10/28), ErbB2 (4/28) or ErbB4 (3/28). By comparison, overexpression, as indicated by inc reased staining intensity, was observed in invasive tumours for EGFR (18/32 ), ErbB2 (8/32), ErbB4 (3/32), and ErbB3 (3/32). Statistical evaluation dem onstrated a significant association of EGFR or ErbB2 overexpression with in vasive carcinoma when compared with benign lesions and apparently normal ep ithelium (p=5.2 x 10(-7) and p=5 x 10(-3) respectively). Tumour-specific ov erexpression of ErbB receptors and their co-expression, most frequently inv olving EGFR and ErbB2, in the same cell layer of neoplastic epithelium, imp licate receptor heterodimers in the pathogenesis of oral squamous carcinoma . Copyright (C) 2001 John Wiley & Sons, Ltd.