Tissue expression of transforming growth factor-beta1 and its receptors: correlation with pathologic features and biochemical progression in patients undergoing radical prostatectomy

Urology. 2004 Jun;63(6):1191-7. doi: 10.1016/j.urology.2003.12.015.

Abstract

Objectives: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Disease Progression
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Prostate / cytology
  • Prostate / metabolism
  • Prostate-Specific Antigen / blood
  • Prostatectomy
  • Prostatic Hyperplasia / metabolism
  • Prostatic Hyperplasia / pathology
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / surgery
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / blood*
  • Transforming Growth Factor beta1

Substances

  • Receptors, Transforming Growth Factor beta
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Prostate-Specific Antigen