Tissue expression of transforming growth factor-β 1 and its receptors: correlation with pathologic features and biochemical progression in patients undergoing radical prostatectomy

Abstract

Objectives To determine whether the abnormal expression of transforming growth factor-beta 1 (TGF-β 1) and/or its receptors (TGFβ-RI and TGFβ-RII) is associated with prostate cancer features and progression; and to investigate the relationship between tissue expression of TGFs and blood levels of TGF-β 1. Methods Immunohistochemical staining for TGF-β 1, TGFβ-RI, and TGFβ-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-β 1 levels were also measured. Results TGF-β 1 was overexpressed in 71 (60%) of 118 patients, and TGFβ-RI and TGFβ-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-β 1 and its receptors were 54% and 62%. Abnormal expression of all three TGFs was significantly associated with extracapsular disease. However, only decreased expression of TGFβ-RI and TGFβ-RII was significantly associated with seminal vesicle involvement and greater pathologic Gleason score. Preoperative plasma TGF-β 1 levels were significantly elevated in patients with abnormal expression of TGFs. TGFβ-RI expression and surgical margin status were independently associated with biochemical progression. Conclusions Our results showed that abnormal expression of TGF-β 1 and its receptors is common in prostate cancer. TGF-β 1 overexpression is moderately but significantly associated with a loss of expression of TGFβ-RI and TGFβ-RII. Loss of TGFβ-RI expression is a prognostic marker in patients with prostate cancer.