TGF-b in prostate cancer Reis ST et al. Interestingly, a quantitative analysis revealed a positive association between increased TGF-b1 mRNA levels and elevated Gleason scores (p = 0.002). Although controversial, this finding is consistent with that of a previous study in which TGF-b plasma levels were higher in men with PCa metastases than in healthy men.18 Shariat et al19 also found a strong correlation between elevated plasma TGF-b and prostate cancer progression and the development of metastases in patients with locally advanced disease. Faria et al20 demon- strated that among patients with PCa, the relative levels of TGF-b1 mRNA increased during the late stages of the disease. Some studies have suggested that decreased expression of TGF-b is not entirely necessary, as some tumor cells might escape the inhibitory effects of TGF-b through mutations that could provide a growth advantage over their benign counterparts. It has also been established that both TGF-b receptors (TbR-I and TbR-II) are required for the proper transduction of TGF-b signaling,21 and prostate cancer cells might reduce the expression or function of either TbR-I or TbR-II to escape the growth-inhibiting effects of TGF-b. This loss of sensitivity to TGF-b by its receptors could induce a compensatory overexpression of TGF-b, thereby leading to more aggressive phenotypes.22 Research has suggested that whether TGF-b exerts a tumor-suppressive or oncogenic effect is contextual and/or depends upon the temporal stage of cellular transforma- tion.23 A recent study reported that the activation of TGF-b signaling pathways might be responsible for mediating the epithelial-mesenchymal transition (EMT), thereby enhan- cing the invasiveness and survival of transformed cells.24 Moreover, TGF-b can alter the host-tumor interaction, thus facilitating tumor growth, promoting angiogenesis, and inhibiting the host immune system.9,25 By examining benign tissues from the removed prostates of patients with PCa who were treated by radical prostatect- omy, we observed the same TGF-b expression pattern as in malignant tissue. This result is interesting because it allows us to propose the use of TGF-b as a tumor marker, there- by overcoming the sampling error that commonly occurs in conventional prostate biopsies; however, larger studies should be conducted to further validate our findings. In conclusion, we showed for the first time in clinical specimens that decreased expression of TGF-b is a char- acteristic of prostate cancer and may be related to cancer initiation and promotion; the role of TGF-b as a regulator of cell growth and apoptosis should be confirmed in a wider series. On the other hand, TGF-b superexpression might be related to tumor progression, as it is more highly expressed in more aggressive tumors, and this finding could be explained by mutations that confer resistance to TGF-b receptors. This hypothesis also warrants further experi- mental studies to analyze the potential of TGF-b as a diagnostic or prognostic marker. 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