title: Clinicopathological correlates of Gli1 expression in a population-based cohort of patients with newly diagnosed bladder cancer.
abstract: BACKGROUND
  Dysregulation of the hedgehog signaling pathway has been linked to the development and progression of a variety of different human tumors including cancers of the skin, brain, colon, prostate, blood, and pancreas. We assessed the clinicopathological factors that are potentially related to expression of Gli1, the transcription factor that is thought to be the most reliable marker of hedgehog pathway activation in bladder cancer.
  
  
  METHODS
  Bladder cancer cases were identified from the New Hampshire State Cancer Registry as histologically confirmed primary bladder cancer diagnosed between January 1, 2002, and July 31, 2004. Immunohistochemical analysis was performed on a tissue microarray to detect Gli1 and p53 expression in these bladder tumors. We computed odds ratios (ORs) and their 95% CIs for Gli1 positivity for pathological category using T category (from TNM), invasiveness, and grade with both the World Health Organization 1973 and World Health Organization International Society of Urological Pathology criteria. We calculated hazard ratios and their 95% CI for Gli1 positivity and recurrence for both Ta-category and invasive bladder tumors (T1+).
  
  
  RESULTS
  A total of 194 men and 67 women, whose tumors were assessable for Gli1 staining, were included in the study. No appreciable differences in Gli1 staining were noted by sex, age, smoking status, or high-risk occupation. Ta-category tumors were more likely to stain for Gli1 as compared with T1-category tumors (adjusted OR = 0.38, CI: 0.17-0.87). Similarly, low-grade (grades 1-2) tumors were more likely to stain for Gli1 as compared with high-grade tumors (grade 3) (adjusted OR = 0.44, CI: 0.21-0.93). In a Cox proportional hazards regression analysis, non-muscle-invasive bladder tumors expressing Gli1 were less likely to recur (adjusted hazard ratio = 0.48; CI: 0.28-0.82; P<0.05) than those in which Gli1 was absent.
  
  
  CONCLUSIONS
  Our findings indicate that Gli1 expression may be a marker of low-stage, low-grade bladder tumors and an indicator of a reduced risk of recurrence in this group.
authors.affiliation: Department of Surgery (Urology), Dartmouth-Hitchcock Medical Center, Lebanon, NH.
authors.forename: Einar F
authors.initials: EF
authors.lastname: Sverrisson
authors.affiliation: Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Zens
authors.affiliation: Cancer Biology Section, National Institutes of Health, Bethesda, MD.
authors.forename: Dennis Liang
authors.initials: DL
authors.lastname: Fei
authors.affiliation: Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH.
authors.forename: Angeline
authors.initials: A
authors.lastname: Andrews
authors.affiliation: Department of Pathology (Urology), Dartmouth-Hitchcock Medical Center, Lebanon, NH.
authors.forename: Alan
authors.initials: A
authors.lastname: Schned
authors.affiliation: Molecular Oncology Program, Department of Surgery, University of Miami, Miami, FL.
authors.forename: David
authors.initials: D
authors.lastname: Robbins
authors.affiliation: Department of Community Health, Brown University, Providence, RI.
authors.forename: Karl T
authors.initials: KT
authors.lastname: Kelsey
authors.affiliation: Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, NH.
authors.forename: James
authors.initials: J
authors.lastname: DiRenzo
authors.affiliation: Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Karagas
authors.affiliation: Department of Surgery (Urology), Dartmouth-Hitchcock Medical Center, Lebanon, NH. Electronic address: john.d.seigne@hitchcock.org.
authors.forename: John D
authors.initials: JD
authors.lastname: Seigne
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016017:Odds Ratio; D016016:Proportional Hazards Models; D012042:Registries; D013997:Time Factors; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D000071676:Zinc Finger Protein GLI1
keywords: Bladder neoplasm; Gli1