Characterization of membranous and cytoplasmic EGFR expression in human normal renal cortex and renal cell carcinoma.
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 x 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.
Pu
Yeong-Shiau
YS
Department of Urology, National Taiwan University College of Medicine, Taipei, Taiwan, Republic of China. yspu@ntu.edu.tw
Huang
Chao-Yuan
CY
Kuo
Yi-Zih
YZ
Kang
Wang-Yi
WY
Liu
Guang-Yaw
GY
Huang
A-Mei
AM
Yu
Hong-Jeng
HJ
Lai
Ming-Kuen
MK
Huang
Shu-Pin
SP
Wu
Wen-Jeng
WJ
Chiou
Shean-Jaw
SJ
Hour
Tzyh-Chyuan
TC
D000368:Aged; D002292:Carcinoma, Renal Cell / Q000737:chemistry* / Q000209:etiology / Q000401:mortality / Q000601:surgery / Q000648:ultrastructure; D002462:Cell Membrane / Q000737:chemistry*; D003593:Cytoplasm / Q000737:chemistry*; D066246:ErbB Receptors / Q000032:analysis*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007672:Kidney Cortex / Q000737:chemistry* / Q000648:ultrastructure; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000209:etiology / Q000401:mortality / Q000601:surgery / Q000648:ultrastructure; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009392:Nephrectomy; D009928:Organ Specificity
D008565:Membrane Proteins; D009363:Neoplasm Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors