Expression of the Endothelin-axis in the different histologic subtypes of renal cell carcinoma: a tissue microarray analysis.
Endothelin-1 and its receptors ETAR and ETBR, commonly referred to as the Endothelin-axis, are emerging to play a role in cancer. The Endothelin-axis has been shown to be involved in proliferation, angiogenesis and metastasis in various human tumours. To assess the role of the Endothelin-axis in renal cell carcinoma, we analysed its expression in archival tumour tissue of 183 patients. Representative tumour blocks were selected for constructing a tissue microarray. Paraffin sections were assessed immunohistochemically using monoclonal and polyclonal antibodies for Endothelin-1, ETAR and ETBR. Staining intensities were analysed semiquantitatively and the results were correlated with various histopathologic factors. Overexpression of Endothelin-1, ETAR and ETBR was identified in 12.8%, 84.1% and 93.3% of cases, respectively. No association with pathological tumour stage and histologic grading was found. Papillary renal cell carcinomas expressed highly significantly more Endothelin-1 than clear cell renal cell carcinomas (34.5% vs. 6.7%, p<0.001), while there was no difference between ETAR- and ETBR-expression in these histologic subtypes. However, ETAR tended to be overexpressed in the subgroup of G3-tumours (p=0.044). Studies are underway assessing the role of the Endothelin-axis and its potential use as a molecular target in renal cell carcinoma.
Herrmann
Edwin
E
Department of Urology, University of Münster, 48149 Münster, Germany. herrmae@ukmuenster.de
Eltze
Elke
E
Bierer
Stefan
S
Bogemann
Martin
M
Brinkmann
Olaf Anselm
OA
Balnowair
Hoda
H
Hertle
Lothar
L
Wulfing
Christian
C
D000911:Antibodies, Monoclonal / Q000737:chemistry; D017209:Apoptosis; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019332:Endothelin-1 / Q000096:biosynthesis; D016232:Endothelins / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D044022:Receptor, Endothelin A / Q000096:biosynthesis; D044023:Receptor, Endothelin B / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D019332:Endothelin-1; D016232:Endothelins; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B