MOLECULAR AND IMMUNOHISTOCHEMICAL STUDY OF CLASS-I GROWTH-FACTOR RECEPTORS IN SQUAMOUS-CELL LUNG CARCINOMAS

The class I growth factor receptor family includes epidermal growth fa ctor receptor, i.e. c-erbB-1, c-erbB-2 and c-erbB-3 molecules. These r eceptors have a significant sequence homology and play an important ro le in cell growth and differentiation. To further investigate their im plication in squamous cell lung carcinomas (SqCLCs), we studied the pr otein expression by immunohistochemistry and examined for possible gen e amplification by a novel semi-quantitative differential polymerase c hain reaction (DPCR) technique. Expression of c-erbB-1, c-erbB-2 and c -erbB-3 was present in 65%, 28% and 10% respectively, of 40 SqCLCs cas es. Seven of the 11 cases that expressed c-erbB-2, was well as all 4 c -erbB-3 expressing cases, also stained with the anti-c-erbB-1 mAb. Exp ression of c-erbB-1, but not c-erbB-2 or c-erbB-3, correlated with the grade of tumor differentiation (100%, 64% and 36% positive cases of w ell, moderately and poorly differentiated cases respectively, p < 0.00 3). In addition, c-erbB-1 expression correlated with the presence of r egional lymph node metastases within the moderately differentiated gro up. The c-erbB-1 gene was amplified in 11/40 (28%) cases, all of which overexpressed c-erbB-1 protein, while c-erbB-2 gene amplification was detected in only one case. There was no c-erbB-3 gene amplification i n any of the 40 SqCLCs cases. These findings suggest that c-erbB-1, c- erbB-2 and c-erbB-3 receptors do not have a common role and are of dif ferent physiological importance, at least at the stage of clinically o vert tumor in human SqCLCs.