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EGFR is overexpressed in the majority of clear cell renal cell carcinomas (CCRCCs). Although EGFR deregulation was found to be of great significance in CCRCC biology, the EGFR
overexpression is not associated with EGFR-targeted therapy responsiveness. Moreover, the prognostic role of EGFR expression remains controversial. In the present study, we evaluated the role
played by EGFR overexpression in CCRCC and its prognostic significance associated with different
immunohistochemical localization patterns. In our study, the Total Score (TS) related to membranouscytoplasmic EGFR expression showed a significant correlation with grade, pathologic stage (pT),
and Stage, Size, Grade, and Necrosis (SSIGN) score, and a negative correlation with nuclear EGFR
expression. No significant correlations were shown between nuclear EGFR and clinic-pathological
features. Additionally, a correlation between SGLT1 expression levels and pT was described. Multivariate analysis identifies pT and SSIGN score as independent prognostic factors for CCRCC. A
significantly increased survival rate was found in the case of positive expression of nuclear EGFR
and SGLT1. Based on our findings, SGLT1 and nuclear EGFR overexpression defines a subgroup of
CCRCC patients with good prognosis. Membranous-cytoplasmic EGFR expression was shown to be
a poor prognostic factor and could define a CCRCC subgroup with poor prognosis that should be
responsive to anti-EGFR therapies