Coexpression patterns of EGFR, HER2, HER3 and HER4 in non-melanoma skin cancer

The receptor tyrosine kinases (RTKs) epidermal growth factor receptor (EGFR ), HER2, HER3 and HER4 are involved in the pathogenesis of multiple human m alignant neoplasias. However, their role in the carcinogenesis of basal cel l carcinomas (BCC) and squamous cell carcinomas (SCC) remains to be elucida ted. In order to further define the role of these RTKs, 56 human skin tissu e samples of normal skin, BCC and SCC were studied by conventional and diff erential and quantitative reverse transcriptase-polymerase chain reaction ( rtPCR). EGFR and HER3 were predominantly expressed in the BCCs and SCCs, wh ile HER2 was ubiquitously expressed. HER4 was not expressed in any sample. Since in vitro studies have provided compelling evidence that heterodimer f ormation of these receptors are associated with different signal transducti on processes, coexpression patterns might be decisive for the induction and maintenance of a malignant phenotype. These results confirm this concept: isolated HER2 expression and EGFR/HER2 were predominantly found in normal s kin, while HER2/HER3 and the triple expression of EGFR/HER2/HER3 were seen more frequently in the BCCs and SCCs compared with normal skin (50% and 40% compared with 26%, respectively). The activation of HER3, in addition to E GFR and HER2, might therefore be associated with the malignant phenotype. H owever, due to the small numbers in this study, further confirmation of the patterns is needed. (C) 2001 Elsevier Science Ltd. All rights reserved.