Angiotensin II type 1 receptor expression and microvessel density in human bladder cancer

Urology. 2011 Apr;77(4):1009.e19-25. doi: 10.1016/j.urology.2010.11.002. Epub 2011 Feb 5.


Objectives: To determine whether angiotensin II type 1 receptor (AT1R) expression and tumor angiogenesis in human bladder cancer (BCa) specimens acquired by transurethral resection (TUR). It has recently been reported that AT1R is expressed in several tumors and is involved in tumor angiogenesis. However, no study has investigated AT1R expression in association with angiogenesis in clinical specimens of bladder cancer.

Methods: Surgical specimens were obtained from 108 patients who had undergone TUR for bladder cancer. All specimens were pathologically diagnosed as urothelial carcinoma. AT1R expression and microvessel density (MVD) were determined by immunostaining. The clinical and pathologic characteristics were retrospectively reviewed.

Results: The MVD was greater in muscle-invasive BCa (MIBC; 29 cases, 34.4 ± 4.1/0.25 mm(2)) than in non-MIBC (NMIBC; 79 cases, 17.4 ± 1.1/0.25 mm(2), P < .0001). AT1R expression was greater in the MIBC (P = .0004) and high-grade (P = .0063) specimens than in the NMIBC and low-grade specimens. In addition, the greater expression of AT1R was significantly associated with MVD (P < .05). In NMIBC, the factors significantly affecting recurrence-free survival on univariate analysis were AT1R (P = .02), MVD (P < .0001), tumor multiplicity (P = .0007), and bacille Calmette-Guérin intravesical instillation after TUR (P = .0026). Multivariate analysis revealed that tumor multiplicity and no BCG intravesical instillation after TUR were independent predictors of 5-year recurrence-free survival, and AT1R and MVD were independent predictors of 1-year recurrence-free survival (P < .01).

Conclusions: AT1R expression and MVD were related to early intravesical recurrence in NMIBC. The results suggest that AT1R could become a new molecular target and a prognostic factor for NMIBC.

MeSH terms

  • Antigens, CD34 / metabolism
  • BCG Vaccine / therapeutic use
  • Cell Count
  • Humans
  • Immunohistochemistry
  • Microvessels / cytology*
  • Neovascularization, Pathologic
  • Prognosis
  • Receptor, Angiotensin, Type 1
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology


  • Antigens, CD34
  • BCG Vaccine
  • Receptor, Angiotensin, Type 1