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. 2021 Aug 14;22(16):8747.
doi: 10.3390/ijms22168747.

Prognostic Impact of Membranous/Nuclear Epidermal Growth Factor Receptor Localization in Clear Cell Renal Cell Carcinoma

Maria Rosaria Muroni  1 , Silvia Ribback  2 , Giovanni Sotgiu  1 , Nils Kroeger  3 , Laura Saderi  1 , Andrea Angius  4 , Paolo Cossu-Rocca  1   5 , Maria Rosaria De Miglio  1
Affiliations

Prognostic Impact of Membranous/Nuclear Epidermal Growth Factor Receptor Localization in Clear Cell Renal Cell Carcinoma

Maria Rosaria Muroni et al. Int J Mol Sci. .

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.

Keywords: SGLT1; clear cell renal cell carcinoma; membranous-cytoplasmic EGFR; nuclear EGFR; prognosis; survival.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Morphologic and immunohistochemical features of Clear Cell Renal Cell Carcinoma. (A) Hematoxylin and Eosin stain shows typical CCRCC morphologic features; (B) Immunohistochemistry for EGFR (clone 2-18C9) displaying diffuse and intense membranous immunoreactivity; (C) Immunohistochemistry for EGFR (polyclonal sc-03) displaying intense nuclear immunoreactivity; (D) Immunohistochemistry for SGLT1 on CCRCC showing diffuse and intense, predominantly membranous immunoreactivity.
Figure 2
Figure 2
Kaplan–Meier curves for overall survival. (A) distribution of overall survival (B) overall survival according to absence/presence of immunostaining for membranous-cytoplasmic EGFR (C) overall survival according to three TS-EGFR groups, (D) overall survival according to absence/presence of immunostaining for nuclear EGFR, (E) overall survival according to absence/presence of immunostaining for SGLT1.
See this image and copyright information in PMC

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