title: Immunohistochemical evidence of the prognostic value of hedgehog pathway components in primary gallbladder carcinoma.
abstract: OBJECTIVE
  The activation of hedgehog (Hh) pathways has been studied extensively in many malignant tumors to elucidate their clinical diagnostic and prognostic utilities. However, their roles in primary gallbladder carcinoma (GBC) remain poorly understood. This study was conducted to clarify the immunoreactivity and prognostic value of Hh pathway components in GBC.
  
  
  METHODS
  Levels of sonic hedgehog (Shh), its receptor, Patched (Ptch1), and its downstream transcription factor, Gli1 protein, were measured by immunohistochemistry in 93 specimens from patients with GBC. We analyzed the correlations between the expression of these factors and clinicopathological features, including prognosis.
  
  
  RESULTS
  Among the 93 GBC specimens, 76 (81.7%), 70 (75.3%) and 66 (70.0%) were positive for Shh, Ptch1 and Gli1 expression, respectively. Expressions were significantly correlated with stage, lymph node metastasis, venous invasion, hepatic infiltration and lymphatic invasion (all P < 0.05). Patients with positive staining for Shh, Ptch1 and Gli1 had significantly lower survival rates than patients with negative staining. The expression patterns of Shh, Ptch1 and Gli1 were all associated with a malignant behavior risk category in GBC.
  
  
  CONCLUSIONS
  To our knowledge, this is the first report to define the role of the Hh pathway in GBC. Shh, Ptch1 and Gli1 are frequently expressed in GBC and associated with poorer survival. Thus, high expressions of Shh, Ptch1 and Gli1 proteins could serve as auxiliary parameters for predicting the malignant behavior of GBC.
authors.affiliation: Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, People's Republic of China.
authors.forename: Jinmao
authors.initials: J
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.forename: Jianguo
authors.initials: J
authors.lastname: Lu
authors.forename: Yizhan
authors.initials: Y
authors.lastname: Cao
authors.forename: Nuan
authors.initials: N
authors.lastname: Song
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Rui
authors.initials: R
authors.lastname: Dong
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Zang
authors.forename: Xilin
authors.initials: X
authors.lastname: Du
authors.forename: Shengzhi
authors.initials: S
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D005706:Gallbladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016019:Survival Analysis; D014157:Transcription Factors / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1
chemical_list: D014408:Biomarkers, Tumor; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; C509239:SHH protein, human; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1