CLINICS 2011;66(7):1143-1147 TGF-b in prostate cancer Reis ST et al. Figure 1 - Quantitative expression of TGF-b1 messenger RNA in malignant prostatic tissue compared with BPH. Fold change in expression was calculated using the 2-DDCT method. to preoperative PSA values, the median TGF-b1 expression levels were also similar (p = 0.5110) between patients with PSA levels $10 ng/ml (6.7610-1-fold) and patients with PSA levels ,10 (5.5610-1-fold). We found an overexpression of TGF-b1 in 26 cases, of which 21 (80.7%) had a Gleason score $7, 13 (50%) had a PSA level $10 ng/ml, 12 (46%) were staged as pT3 and 9 (35%) had biochemical recurrence. Only 2 (7.7%) of the patients with TGF-b1 overexpression exhibited no unfavor- able prognostic factors. We also evaluated the expression levels of TGF-b1 in patients with biochemical recurrence (which was defined as a PSA level above 0.4 ng/ml) at a mean follow-up period of 60 months. Median TGF-b1 expression levels were statistically Table 2 - Relative expression of the TGF-b1 gene in the malignant prostatic tissues according to Gleason score, pathologic stage, PSA level and biochemical recurrence. Fold changes in gene expression were calculated using the DDCT method (QRel = 2-DDCT). Gleason Score ,7 (n = 32) $7 (n = 36) p-value Pathologic Stage pT2 (n = 37) pT3 (n = 40) p-value PSA Level ,10 (n = 45) $10 (n = 33) p-value Biochemical Recurrence Without (n = 29) With (n = 28) p-value TGF-b1 0.46 (0.02 - 6.20) 0.93 (0.02 - 33.3) 0.006 0.65 (0.02 - 33.3) 0.48 (0.04 - 18.9) 0.249 0.55 (0.04 - 33.3) 0.67 (0.02 - 14.3) 0.508 0.60 (1.12 - 33.3) 0.54 (0.04 - 18.9) 0.523 1145 similar (p = 0.528) among patients with and without recur- rence (5.4610-1 and 6.1610-1, respectively). We performed a multivariate analysis, and the Gleason score was the unique independent prognostic factor in our series (p = 0.022). Additionally, we tested the expression of TGF-b1 in the prostatic tissues from 10 patients with benign PCa and found the same expression patterns as observed in the malignant tissues (median 1.7610-1) (p = 0.05). DISCUSSION In this study, we found that TGF-b1 was underexpressed in malignant prostatic tissue as compared to BPH samples (median 7610-1-fold). Thus, we may assume that TGF-b contributes to the development of prostate cancer by acting as an inhibitor of cell proliferation and an inducer of apopto- sis.8,9 Furthermore, we identified higher TGF-b expression levels in tumors with higher Gleason scores, suggesting that this gene may play a role in PCa progression and prognosis. Soulitzis et al10 also reported a decrease in TGF-b expression in PCa. TGF-b is generally a growth inhibitor of both benign prostatic epithelial cells11 and prostate cancer cells in vitro12 and has been shown to inhibit proliferation and induce apoptosis in prostatic epithelial cells.8,13 Moreover, TGF-b stimulates the synthesis of collagen, fibronectin, and integrins, and it inhibits matrix degradation through the downregulation of proteinases such as collage- nases, stromelysins, and plasminogen activators.14 Paired with its downregulation of proteinases, TGF-b upregulates protei- nase inhibitors such as the following endogenous matrix metalloproteinases (MMP) inhibitors: the tissue inhibitor of metalloproteinase-1 (TIMP-1)15 and plasminogen activator inhibitor-1.16 TGF-b also acts as a repressor of matrix metalloproteinase expression through the TGF-b inhibitory element (TIE), which is found in the 59-flanking region of several genes in the MMP family, namely interstitial collage- nase (MMP-1) and 92-kDa type IV collagenase (MMP-9).17