Membranous expression and prognostic implications of epidermal growth factor receptor protein in human renal cell cancer.
BACKGROUND
It has been indicated that altered expression of the epidermal growth factor receptor (EGFR) promotes the invasive and metastatic potential of a variety of human malignancies. Therefore, the aim of the present study was to determine EGFR expression in clear cell renal cell carcinomas (RCC) to evaluate its prognostic relevance for the clinical course of the disease.


METHODS
EGFR protein expression, detected by immunohistochemistry and tissue microarray analysis (TMA), was investigated in a cohort of 149 randomly selected patients subjected to tumor nephrectomy for RCC.


RESULTS
The tumor cells preferably exhibited a homogeneous membrane-bound reactivity for EGFR; EGFR overexpression was detected in 70 (47%) of the primary tumor specimens, but in only 12 (9%) of the benign tissue samples (p<0.0001; Fisher's t-test). Tumor-associated EGFR staining was stratified into three groups: I: low staining score (n=75, 50%); II: intense expression (n=56, 38%); and III: strong overexpression (n = 18, 12%). Strong reactivity for EGFR was identified as predicting the patients' survival both during uni- and multivariate analysis (p=0.03). Interestingly, the overall survival of the intense expression group surpassed even the low expression group (p=0.023).


CONCLUSIONS
The observation that primary RCC specimens exhibit EGFR at higher levels when compared with benign renal parenchyma indicates its role in tumor development and progression. The availability of more refined prognostic factors would assist decision making in terms of the value of more aggressive treatment options for prognostically defined subgroups of patients. Additionally, if overexpression of EGFR identifies RCC with a more aggressive biological behavior, the latter receptor might serve as a novel target for a more effective therapeutical approach to RCC.
Merseburger
Axel S
AS
Department of Urology, Eberhard Karls University Tuebingen, Hoppe-Seyler-Str. 3, 72076, Tuebingen, Germany.
Hennenlotter
Jörg
J
Simon
Perikles
P
Kruck
Stephan
S
Koch
Eva
E
Horstmann
Marcus
M
Kuehs
Ursula
U
Küfer
Rainer
R
Stenzl
Arnulf
A
Kuczyk
Markus A
MA
D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism; D015331:Cohort Studies; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate
D066246:ErbB Receptors