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
