title: 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.
abstract: 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.
authors.affiliation: Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Tae-Jung
authors.initials: TJ
authors.lastname: Kim
authors.forename: Ji Youl
authors.initials: JY
authors.lastname: Lee
authors.forename: Tae-Kon
authors.initials: TK
authors.lastname: Hwang
authors.forename: Chang Suk
authors.initials: CS
authors.lastname: Kang
authors.forename: Yeong-Jin
authors.initials: YJ
authors.lastname: Choi
mesh_terms: D000328:Adult; D000368:Aged; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D000072079:Patched Receptors; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000556:secondary* / Q000601:surgery; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D012189:Retrospective Studies; D015398:Signal Transduction; D000072086:Smoothened Receptor; D015996:Survival Rate; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012097:Repressor Proteins; C509239:SHH protein, human; C491023:SMO protein, human; C490764:SUFU protein, human; D000072086:Smoothened Receptor; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D017430:Prostate-Specific Antigen