Predictive value of expression of transforming growth factor-β1 and its receptors in transitional cell carcinoma of the urinary bladder

Abstract

BACKGROUND. The purpose of this study was to describe the expression patterns of transforming growth factor (TGF)-β1 and its receptors in transitional cell carcinoma (TCC) of the bladder, to investigate the relation between the TGF-β1 and its receptors, and to determine whether altered expression of TGF-β or its receptors is associated with disease progression and survival in patients with TCC of the bladder. METHODS. Immunohistochemical staining for TGF-β1 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-β1, TGF-β-RI, and TGF-β-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-βs, and 26 (33%) had altered expression of all 3. Expression of the three TGF-βs was highly concordant (P < 0.018). Loss of expression of TGF-β-RI or TGF-β-RII was associated with invasive tumor stage (P<0.001), high grade (P<0.006), and lymphovascular invasion (P<0.030). Overexpression of TGF-β1 was associated with invasive tumor stage only (P=0.024). With a median follow-up of 101 months, TGF-βRI was an independent predictor of both disease progression (P=0.007) and disease specific survival (P=0.006) whereas TGF-β1 was an independent predictor of disease progression only (P=0.050). Transforming growth factor-β-RII was not independently associated with either disease progression or survival. CONCLUSIONS. Altered expression of TGF-β1 and its receptors is common in TCC of the bladder. Overexpression of TGF-β1 is associated with the loss of expression of its receptors. Transforming growth factor - β1 and TGF-β-RI are independently associated with clinical outcome in patients with bladder TCC treated by radical cystectomy.© 2001 American Cancer Society.