Department of Medical, Surgical and Experimental Sciences, University of Sassari, Via P. Manzella, 4, 07100 Sassari, Italy.
Institut fuer Pathologie, Universitaetsmedizin Greifswald, Friedrich-Loeffler-Str. 23e, 17475 Greifswald, Germany.
Int J Mol Sci. 2021 Aug 14;22(16):8747. doi: 10.3390/ijms22168747.
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.
表皮生长因子受体（EGFR）在大多数透明细胞肾细胞癌（ccRCC）中过表达。尽管 EGFR 失调在 ccRCC 生物学中具有重要意义，但 EGFR 过表达与 EGFR 靶向治疗反应无关。此外，EGFR 表达的预后作用仍存在争议。在本研究中，我们评估了 EGFR 过表达在 ccRCC 中的作用及其与不同免疫组织化学定位模式相关的预后意义。在我们的研究中，与膜细胞质 EGFR 表达相关的总评分（TS）与分级、病理分期（pT）和分期、大小、分级和坏死（SSIGN）评分显著相关，与核 EGFR 表达呈负相关。核 EGFR 与临床病理特征之间无显著相关性。此外，还描述了 SGLT1 表达水平与 pT 之间的相关性。多因素分析确定 pT 和 SSIGN 评分是 ccRCC 的独立预后因素。核 EGFR 和 SGLT1 阳性表达的患者生存率显著提高。根据我们的研究结果，SGLT1 和核 EGFR 过表达定义了 ccRCC 患者具有良好预后的亚组。膜细胞质 EGFR 表达是预后不良的因素，并可定义对抗 EGFR 治疗有反应的预后不良的 ccRCC 亚组。
