Expression of the endothelin axis in bladder cancer: relationship to clinicopathologic parameters and long-term survival.
OBJECTIVE
Endothelin-1 (ET-1) and its receptors ET(A)R and ET(B)R, referred to as the Endothelin-axis, play an emerging role in cancer. We examined the ET-axis immunohistochemically in invasive bladder cancer.


METHODS
Tumor specimens from 157 patients after cystectomy were stained immunohistochemically for ET-1, ET(A)R and ET(B)R. After semiquantitative analysis the staining results were correlated with clinicopathological parameters and survival rates.


RESULTS
Overexpression of ET-1, ET(A)R and ET(B)R was identified in 26.8%, 58.8% and 76.9% of cases, respectively. No association with TNM staging and histologic grading was found. However, patients with ET(B)R expression tended to have organ-confined tumors (p=0.16) and no vascular invasion (p=0.09), the latter being statistically significant in the subgroup of G3 tumors (p=0.02). ET(B)R overexpression was associated with favorable disease-free survival (p=0.04).


CONCLUSIONS
The ET-axis is overexpressed in bladder cancer, ET(B)R predominating in this entity and being associated with a more favorable prognosis. Further studies are warranted to elucidate the role of the ET-axis as a molecular target in bladder cancer.
Wülfing
Christian
C
Department of Urology, University of Münster, Albert-Schweitzer Strasse 33, 48129 Münster, Germany. wulfing@uni-muenster.de
Eltze
Elke
E
Yamini
Johann
J
Wülfing
Pia
P
Bierer
Stefan
S
Böcker
Werner
W
Hertle
Lothar
L
Semjonow
Axel
A
Sievert
Karl-Dietrich
KD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D015653:Cystectomy; D018572:Disease-Free Survival; D019332:Endothelin-1 / Q000096:biosynthesis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D044022:Receptor, Endothelin A / Q000096:biosynthesis*; D044023:Receptor, Endothelin B / Q000096:biosynthesis*; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery
D014408:Biomarkers, Tumor; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B