Hedgehog signaling protein expression and its association with prognostic parameters in prostate cancer: A retrospective study from the view point of new 2010 anatomic stage/prognostic groups

Background: The expression of Hedgehog (Hh) signaling pathway in prostate cancer is well-known but its clinicopathologic role has not been elucidated well. Methods: Prostatectomy cases of prostate cancer (n = 155) were prepared and assessed by clinicopathologic parameters including new 2010 anatomic stage/prognostic groups (ASPG) of prostate cancer. The expression of five Hh signaling proteins including Sonic hedgehog (Shh), Patched, Smoothened, and GLIoma-associated oncogene, in addition with Suppressor of fused (Su(fu)) were analyzed immunohistochemically. Real-time polymerase chain reaction was performed to assess the mRNA expression status. Results: The expression of each Hh signaling protein was significantly correlated with poor prognostic parameters such as larger tumor size, high pretreatment prostate-specific antigen (PSA), high Gleason score, perineural invasion and new ASPG. Among Hh signaling proteins, Sonic hedgehog and Smoothened expressions tend to have a significantly higher risk of PSA recurrence (P<0.001 and P = 0.011, respectively). Multivariate analysis proved Shh expression as independent prognostic factors of PSA recurrence along with Gleason score, ASPG, tumor volume, and pretreatment PSA. Conclusions: Hh signaling activity is significantly associated with worse prognostic parameters. Shh can be regarded as a poor prognostic factor for PSA recurrence.