The role of the endothelin axis and microvessel density in bladder cancer - correlation with tumor angiogenesis and clinical prognosis.
Endothelin-1 (ET-1) and its receptors, entothelin-A (ETAR) and endothelin-B (ETBR), commonly referred to as the endothelin (ET)-axis, are involved in tumor biology and growth. We investigated the effects of the ET-axis on microvessel density (MVD) and the clinicopathological parameters of patients with invasive bladder cancer. Paraffin tumor sections of 120 patients who had undergone radical cystectomy were assessed immunohistochemically using mono- and polyclonal antibodies for ET-1, ETAR, ETBR and CD34 (MVD). Staining intensities were analyzed semiquantitatively and the MVD was calculated as vessels per field. The results were correlated with various pathological and clinical factors, as well as with disease-free and overall survival. Transitional cell carcinomas (MVD=23.7) were better vascularized than squamous cell carcinomas (MVD=17.8, p=0.04). Organ-confined tumors (MVD=32.2) were better vascularized than T3- and T4-tumors (MVD=21.2, p=0.02) and ET-1 was overexpressed in this subgroup (p=0.027). Patients with metastatic regional lymph nodes (MVD=20.9) tended to have less MVD than patients without regional lymph node metastases (MVD=24.1) (p=0.15). The account of MVD did not reveal any significant differences in disease-free or overall survival. Organ-confined tumors and ET-1 overexpression are associated with upregulated microvessel density. These results suggest that MVD and ET-1 could be considered good prognostic factors.
Herrmann
Edwin
E
Department of Urology, University of Münster, 48149 Münster, Germany. herrmae@ukmuenster.de
Bögemann
Martin
M
Bierer
Stefan
S
Eltze
Elke
E
Toma
Marieta I
MI
Köpke
Thomas
T
Hertle
Lothar
L
Wülfing
Christian
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism / Q000556:secondary; D002295:Carcinoma, Transitional Cell / Q000098:blood supply / Q000378:metabolism / Q000556:secondary; D015653:Cystectomy; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011379:Prognosis; D044022:Receptor, Endothelin A / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000378:metabolism*; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000098:blood supply* / Q000378:metabolism*
D014408:Biomarkers, Tumor; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B