title: Connexin 43 expression predicts poor progression-free survival in patients with non-muscle invasive urothelial bladder cancer.
abstract: OBJECTIVE
  To evaluate the protein expression of connexin 43 (Cx43) in primary urothelial bladder cancer and test its association with the histopathological characteristics and clinical outcome.
  
  
  METHODS
  A tissue microarray containing 348 tissue samples from 174 patients with primary urothelial carcinomas of the bladder was immunohistochemically stained for Cx43. The intensity of staining was semiquantitatively evaluated (score 0, 1+, 2+), and the association with clinicopathological features was assessed. Univariable and multivariable analyses were performed to identify predictors for progression-free survival (PFS).
  
  
  RESULTS
  Membranous Cx43 immunoreactivity was detected in 118 (67.8%) of 174 analysable urothelial carcinomas, of which 31 (17.8%) showed even a strong (score 2+) and mainly homogeneous staining. Strong expression levels of Cx43 (score 2+) were associated with higher tumour grade, multiplicity and increased proliferation (all p<0.05). In the subgroup of patients with stage pTa and pT1 bladder tumours (n=158), strong Cx43 expression (p<0.001), solid growth pattern (p<0.001) and increased Ki-67 proliferation fraction (p<0.05) were significantly associated with shorter PFS in an univariable Cox regression analysis. In multivariable Cox regression models, Cx43 immunoreactivity and histological growth pattern remained highly significant and adverse risk factors for PFS.
  
  
  CONCLUSIONS
  The expression levels of Cx43 are frequent in non-muscle invasive bladder cancer (NMIBC), with high expression levels being associated with poor prognosis. Routine assessment of Cx43 expression may improve the identification of high-risk NMIBC.
authors.affiliation: Department of Urology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Cédric
authors.initials: C
authors.lastname: Poyet
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Buser
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Filip
authors.initials: F
authors.lastname: Roudnicky
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Detmar
authors.affiliation: Department of Urology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hermanns
authors.affiliation: Department of Urology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Doris
authors.initials: D
authors.lastname: Mannhard
authors.affiliation: Department of Urology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Andrej
authors.initials: A
authors.lastname: Höhn
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Rüschoff
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhong
authors.affiliation: Department of Urology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Tullio
authors.initials: T
authors.lastname: Sulser
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wild
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D049109:Cell Proliferation; D018031:Connexin 43 / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D046888:Tissue Array Analysis; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D019459:Urothelium / Q000737:chemistry* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D018031:Connexin 43; C500216:GJA1 protein, human; D019394:Ki-67 Antigen
keywords: BLADDER; TUMOUR MARKERS; URINARY TRACT TUMOURS