Abstract
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 membranous-cytoplasmic 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.
Highlights
Clear cell renal cell carcinoma (CCRCC) is the most aggressive renal cell carcinoma (RCC), representing ~85% of all RCC types
48.3% of CCRCCs were classified as T1, 14.2% as T2, and 37.5% as T3
Our results showed that SSIGN score and tumor size are independent prognostic factors for CCRCC
Summary
Clear cell renal cell carcinoma (CCRCC) is the most aggressive renal cell carcinoma (RCC), representing ~85% of all RCC types. The 20% of patients that undergo nephrectomy may develop metastasis or recurrence during the follow-up [1]. Despite strong advances in therapeutics, survival rates remain poor for metastatic CCRCC due to resistance to chemo- and radiotherapy, including targeted therapies [2]. The introduction of immune checkpoint inhibitors (ICIs, i.e., T-cell checkpoint blockage with PD-1/PDL-1 or CTLA-4 antibodies) as single-agent or in combination with other ICIs, or with recent generation of VEGF tyrosine kinase inhibitors (TKIs), has shown impressive survival benefits in metastatic RCC [3]. The survival benefit provided by first line ICI-TKI combinations vs sunitinib monotherapy has been proved in all metastatic RCC patients regardless of clinico-pathological data [4]
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