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.