Predictive value of expression of transforming growth factor-beta(1) and its receptors in transitional cell carcinoma of the urinary bladder

Cancer. 2001 Sep 15;92(6):1475-83. doi: 10.1002/1097-0142(20010915)92:6<1475::aid-cncr1472>;2-x.


Background: The purpose of this study was to describe the expression patterns of transforming growth factor (TGF)-beta(1) and its receptors in transitional cell carcinoma (TCC) of the bladder, to investigate the relation between the TGF-beta(1) and its receptors, and to determine whether altered expression of TGF-beta or its receptors is associated with disease progression and survival in patients with TCC of the bladder.

Methods: Immunohistochemical staining for TGF-beta(1) and its receptors I and II was conducted on formalin fixed paraffin embedded archival cystectomy specimens of 80 patients with bladder TCC. Immunoreactivity was categorized as either positive or negative in a blinded fashion.

Results: Expression of TGF-beta(1), TGF-beta-RI, and TGF-beta-RII was altered in 51 (64%), 34 (43%), and 38 (48%) specimens, respectively. Sixty (75%) specimens had altered expression of at least 1 of the 3 TGF-betas, and 26 (33%) had altered expression of all 3. Expression of the three TGF-betas was highly concordant (P < 0.018). Loss of expression of TGF-beta-RI or TGF-beta-RII was associated with invasive tumor stage (P < 0.001), high grade (P < 0.006), and lymphovascular invasion (P < 0.030). Overexpression of TGF-beta(1) was associated with invasive tumor stage only (P = 0.024). With a median follow-up of 101 months, TGF-beta-RI was an independent predictor of both disease progression (P = 0.007) and disease specific survival (P = 0.006) whereas TGF-beta(1) was an independent predictor of disease progression only (P = 0.050). Transforming growth factor-beta-RII was not independently associated with either disease progression or survival.

Conclusions: Altered expression of TGF-beta(1) and its receptors is common in TCC of the bladder. Overexpression of TGF-beta(1) is associated with the loss of expression of its receptors. Transforming growth factor-beta(1) and TGF-beta-RI are independently associated with clinical outcome in patients with bladder TCC treated by radical cystectomy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Transitional Cell / chemistry*
  • Carcinoma, Transitional Cell / mortality
  • Carcinoma, Transitional Cell / pathology
  • Cystectomy
  • Humans
  • Immunohistochemistry
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Receptors, Transforming Growth Factor beta / analysis*
  • Transforming Growth Factor beta / analysis*
  • Urinary Bladder Neoplasms / chemistry*
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology


  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta