Predictive value of expression of transforming growth factor-beta(1) and its receptors in transitional cell carcinoma of the urinary bladder.
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.
Kim
J H
JH
Scott Department of Urology, Baylor College of Medicine and the Methodist Hospital, Houston, Texas 77030, USA.
Shariat
S F
SF
Kim
I Y
IY
Menesses-Diaz
A
A
Tokunaga
H
H
Wheeler
T M
TM
Lerner
S P
SP
D002295:Carcinoma, Transitional Cell / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D015653:Cystectomy; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis*; D016212:Transforming Growth Factor beta / Q000032:analysis*; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology
D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta