Tissue expression of transforming growth factor-beta1 and its receptors: correlation with pathologic features and biochemical progression in patients undergoing radical prostatectomy.
OBJECTIVE
To determine whether the abnormal expression of transforming growth factor-beta1 (TGF-beta1) and/or its receptors (TGFbeta-RI and TGFbeta-RII) is associated with prostate cancer features and progression; and to investigate the relationship between tissue expression of TGFs and blood levels of TGF-beta1.


METHODS
Immunohistochemical staining for TGF-beta1, TGFbeta-RI, and TGFbeta-RII was carried out on archival specimens from 118 consecutive patients who underwent radical prostatectomy for clinically localized disease (median follow-up 57.5 months). Preoperative plasma TGF-beta1 levels were also measured.


RESULTS
TGF-beta1 was overexpressed in 71 (60%) of 118 patients, and TGFbeta-RI and TGFbeta-RII expression was decreased in 34 (29%) and 39 (33%) of 118 patients, respectively. Of the 118 patients, 82 (70%) had abnormal expression of at least one of the three TGFs and 22 (19%) had abnormal expression of all three. The concordance rates between the expression of TGF-beta1 and its receptors were 54% and 62%. Abnormal expression of all three TGFs was significantly associated with extracapsular disease. However, only decreased expression of TGFbeta-RI and TGFbeta-RII was significantly associated with seminal vesicle involvement and greater pathologic Gleason score. Preoperative plasma TGF-beta1 levels were significantly elevated in patients with abnormal expression of TGFs. TGFbeta-RI expression and surgical margin status were independently associated with biochemical progression.


CONCLUSIONS
Our results showed that abnormal expression of TGF-beta1 and its receptors is common in prostate cancer. TGF-beta1 overexpression is moderately but significantly associated with a loss of expression of TGFbeta-RI and TGFbeta-RII. Loss of TGFbeta-RI expression is a prognostic marker in patients with prostate cancer.
Shariat
Shahrokh F
SF
Baylor Prostate Center, Scott Department of Urology, Baylor College of Medicine and Methodist Hospital, Houston, Texas 77030, USA.
Menesses-Diaz
Andres
A
Kim
Isaac Y
IY
Muramoto
Masatoschi
M
Wheeler
Thomas M
TM
Slawin
Kevin M
KM
D000328:Adult; D000368:Aged; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011467:Prostate / Q000166:cytology / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000097:blood*; D053773:Transforming Growth Factor beta1
D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017430:Prostate-Specific Antigen