Analysis of EGFR kinase-dependent and kinase-independent roles in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (CCRCC) has been widely investigated for EGFR protein expression, a common occurrence in CCRCCs. Although recent studies claimed for its potential prognostic significance. Nonetheless, genetic evidences of EGFR gene activating mutations and/or gene amplification have been rarely confirmed in the literature, thus supporting clinical trials data which established that the treatment with Tyrosine kinase inhibitors is not effective for CCRCC. New evidences have been given about the interactions between EGFR and SGLT1, independently of its kinase activity. Aim of our study was to perform an extensive investigation of genetic changes and functional kinase activities in a series of EGFR-positive CCRCCs, and to elucidate the correlation between EGFR and SGLT1 protein expressions. Our study demonstrates that EGFR protein overexpression is a recurrent event in CCRCCs and gene expression profile shows the presence of gene overexpression only in the 38.2% of CCRCCs. FISH analysis reveal the absence of EGFR amplification and high polysomy of chromosome 7. Moreover our data showed that SGLT1 is frequently overexpressed in CCRCC EGFR-positive. Since the activation of downstream EGFR pathways is found in about 77% of SGLT1-positive CCRCC, it is conceivable that the EGFR kinase and non-kinase functions can be carried out independently of each other. Therefore the interaction between EGFR/SGLT1 might be a novel therapeutic target for cancer treatment.