title: p63 expression defines a lethal subset of muscle-invasive bladder cancers.
abstract: BACKGROUND
  p63 is a member of the p53 family that has been implicated in maintenance of epithelial stem cell compartments. Previous studies demonstrated that p63 is downregulated in muscle-invasive bladder cancers, but the relationship between p63 expression and survival is not clear.
  
  
  RESULTS
  We used real-time PCR to characterize p63 expression and several genes implicated in epithelial-to-mesenchymal transition (EMT) in human bladder cancer cell lines (n = 15) and primary tumors (n = 101). We correlated tumor marker expression with stage, disease-specific (DSS), and overall survival (OS). Expression of E-cadherin and p63 correlated directly with one another and inversely with expression of the mesenchymal markers Zeb-1, Zeb-2, and vimentin. Non-muscle-invasive (Ta and T1) bladder cancers uniformly expressed high levels of E-cadherin and p63 and low levels of the mesenchymal markers. Interestingly, a subset of muscle-invasive (T2-T4) tumors maintained high levels of E-cadherin and p63 expression. As expected, there was a strongly significant correlation between EMT marker expression and muscle invasion (p<0.0001). However, OS was shorter in patients with muscle-invasive tumors that retained p63 (p = 0.007).
  
  
  CONCLUSIONS
  Our data confirm that molecular markers of EMT are elevated in muscle-invasive bladder cancers, but interestingly, retention of the "epithelial" marker p63 in muscle-invasive tumors is associated with a worse outcome.
authors.affiliation: Department of Urology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Woonyoung
authors.initials: W
authors.lastname: Choi
authors.forename: Jay B
authors.initials: JB
authors.lastname: Shah
authors.forename: Mai
authors.initials: M
authors.lastname: Tran
authors.forename: Robert
authors.initials: R
authors.lastname: Svatek
authors.forename: Lauren
authors.initials: L
authors.lastname: Marquis
authors.forename: I-Ling
authors.initials: IL
authors.lastname: Lee
authors.forename: Dasom
authors.initials: D
authors.lastname: Yu
authors.forename: Liana
authors.initials: L
authors.lastname: Adam
authors.forename: Sijin
authors.initials: S
authors.lastname: Wen
authors.forename: Yu
authors.initials: Y
authors.lastname: Shen
authors.forename: Colin
authors.initials: C
authors.lastname: Dinney
authors.forename: David J
authors.initials: DJ
authors.lastname: McConkey
authors.forename: Arlene
authors.initials: A
authors.lastname: Siefker-Radtke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D030541:Databases, Genetic; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009132:Muscles / Q000473:pathology*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000145:classification* / Q000201:enzymology / Q000235:genetics / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D020780:Matrix Metalloproteinase 9