Characterization of membranous and cytoplasmic EGFR expression in human normal renal cortex and renal cell carcinoma

Yeong-Shiau Pu,Wen-Jeng Wu,Shean-Jaw Chiou,Hong-Jeng Yu,Wang-Yi Kang,Tzyh-Chyuan Hour,A-Mei Huang,Guang-Yaw Liu,Yi-Zih Kuo,Chao-Yuan Huang,Ming-Kuen Lai,Shu-Pin Huang

doi:10.1186/1423-0127-16-82

Abstract

Metastatic renal cell carcinoma (RCC) is highly resistant to conventional systemic treatments, including chemotherapy, radiotherapy and hormonal therapies. Previous studies have shown over-expression of EGFR is associated with high grade tumors and a worse prognosis. Recent studies suggest anticancer therapies targeting the EGFR pathway have shown promising results in clinical trials of RCC patients. Therefore, characterization of the level and localization of EGFR expression in RCC is important for target-dependent therapy. In this study, we investigated the clinical significance of cellular localization of EGFR in human normal renal cortex and RCC. RCC and adjacent normal kidney tissues of 63 patients were obtained for characterization of EGFR expression. EGFR protein expression was assessed by immunohistochemistry on a scale from 0 to 300 (percentage of positive cells × staining intensity) and Western blotting. EGFR membranous staining was significantly stronger in RCC tumors than in normal tissues (P < 0.001). In contrast, EGFR cytoplasmic staining was significantly higher in normal than in tumor tissues (P < 0.001). The levels of membranous or cytoplasmic EGFR expression in RCC tissues were not correlated with sex, tumor grade, TNM stage or overall survival (P > 0.05). These results showed abundant expression of membranous EGFR in RCC, and abundant expression of cytoplasmic EGFR in normal tissues. EGFR expression in RCC was mostly located in the cell membrane, whereas the EGFR expression in normal renal tissues was chiefly seen in cytoplasm. Our results suggest different locations of EGFR expression may be associated with human renal tumorigenesis.

Highlights

Renal cell carcinoma (RCC) arises mainly from renal tubular epithelia [1]
Metastatic renal cell carcinoma (RCC) is highly resistant to conventional systemic treatments, including chemotherapy, radiotherapy and about 10-20% of patients respond to cytokine-based immunotherapy [3]
We demonstrated the different locations of epidermal growth factor receptor (EGFR) immunostaining in renal tumorigenesis from renal cell carcinoma (RCC) and adjacent normal kidney tissues of 63 patients

Summary

Introduction

Renal cell carcinoma (RCC) arises mainly from renal tubular epithelia [1]. Metastatic RCC is highly resistant to conventional systemic treatments, including chemotherapy, radiotherapy and about 10-20% of patients respond to cytokine-based immunotherapy [3]. Development of targeted therapies in renal cell cancer is largely due to the fact that a growing understanding of the underlying molecular biology of RCC has established the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways as relevant therapeutic targets in RCC [3,4]. Despite the treatments available most patients die of metastatic disease. Many studies have demonstrated genetic and environmental factors lead to RCC occurring during a protracted period of tumorigenesis [4]. It seemed desirable to identify and characterize potential molecular markers appearing during of tumorigenesis which might provide rapid and effective possibilities for early detection of RCC [5]

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Conclusion