title: Loss of APKC expression independently predicts tumor recurrence in superficial bladder cancers.
abstract: OBJECTIVE
  Epithelial-mesenchymal transition (EMT) is known to play an important role in the development of tumor invasion and progression in tumors of epithelial origin. Our aim was to investigate the role of tight junction proteins, Par3/Par6/atypical protein kinase C (APKC), Discs large (Dlg), and Scribble in human bladder pathogenesis.
  
  
  METHODS
  We evaluated levels of APKC, Dlg, and Scribble in 92 superficial bladder tumors using tissue microarrays and immunohistochemistry, and correlated expression with pathologic variables and clinical outcomes.
  
  
  RESULTS
  There was a slight apparent enrichment in strong vs. weak staining for APKC (54.9% vs. 45.1%), Dlg (65.7% vs. 34.3%), and a marked enrichment for Scribble (75% vs. 25%) in the superficial bladder tumors. Univariate analysis determined that both tumor focality and APKC expression were significantly associated with tumor recurrence (P < 0.05). Multivariate analysis using the Cox's proportional hazards model revealed that only APKC (P = 0.025) as well as tumor focality (P = 0.018) were independent and significant prognostic factors for tumor recurrence in all patients. We found that no immunohistochemical staining of any of the cell polarity proteins significantly predicted for tumor progression on either univariate or multivariate analysis.
  
  
  CONCLUSIONS
  Loss of APKC expression in superficial bladder tumors is a strong predictor of tumor recurrence.
authors.affiliation: Department of Surgery, Division of Urology, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Namdarian
authors.forename: Edwin
authors.initials: E
authors.lastname: Wong
authors.forename: Ryan
authors.initials: R
authors.lastname: Galea
authors.forename: John
authors.initials: J
authors.lastname: Pedersen
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Chin
authors.forename: Robert
authors.initials: R
authors.lastname: Speirs
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Humbert
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Costello
authors.forename: Niall M
authors.initials: NM
authors.lastname: Corcoran
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Hovens
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D000074288:Discs Large Homolog 1 Protein; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000706:statistics & numerical data; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000378:metabolism*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011493:Protein Kinase C / Q000096:biosynthesis*; D046888:Tissue Array Analysis; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; D008565:Membrane Proteins; C509689:PARD3 protein, human; C499657:PARD6A protein, human; C480591:SCRIB protein, human; D025521:Tumor Suppressor Proteins; C115015:PKC-3 protein; D011493:Protein Kinase C