title: TRAIL and osteoprotegerin (OPG) expression in bladder urothelial carcinoma:  correlation with clinicopathological parameters and prognosis.
abstract: To investigate the expression of tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and osteoprotegerin (OPG) in bladder urothelial carcinomas (UCs) and assess possible interrelations with other regulators of TRAIL induced apoptosis (p65/NF-κB, p-ERK1/2, p-AKT) and FGFR3, as well as to elucidate their potential involvement in bladder tumourigenesis and determine their potential prognostic utility.
  
  
  
  Paraffin embedded transurethral resection tissue from 128 patients with UC was immunostained for TRAIL and OPG as well as for p65/NF-κB, p-ERK1/2, p-AKT and FGFR3.
  
  
  
  TRAIL and OPG were coexpressed in 96.6% of cases and positively interrelated. OPG expression was significantly different among histological grades, being higher in low-grade UCs and was inversely correlated with the presence of lymphovascular invasion (LVI). TRAIL also displayed an inverse relationship with histological grade, T-category and LVI. Both OPG and TRAIL expression were positively correlated with FGFR3 expression, the former relationship being marginal. Moreover, increased TRAIL expression was marginally correlated with lower NF-κB/p65 nuclear expression. Increased OPG expression adversely affected survival both in univariate and multivariate analysis.
  
  
  
  OPG and TRAIL are frequently expressed and coexpressed in UCs, supporting the involvement of OPG in the resistance to TRAIL-driven apoptosis. Inhibition of NF-κB activation may also play a similar role, although less important. OPG emerged as an independent prognostic marker of adverse significance.
authors.affiliation: First Department of Pathology, Laiko General Hospital, Athens, University School of Medicine, Athens, Greece. glevidou@yahoo.gr
authors.forename: Georgia
authors.initials: G
authors.lastname: Levidou
authors.forename: Irene
authors.initials: I
authors.lastname: Thymara
authors.forename: Angelica A
authors.initials: AA
authors.lastname: Saetta
authors.forename: Polyanthi
authors.initials: P
authors.lastname: Papanastasiou
authors.forename: Petros
authors.initials: P
authors.lastname: Pavlopoulos
authors.forename: Stratigoula
authors.initials: S
authors.lastname: Sakellariou
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Fragkou
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou
mesh_terms: D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D053715:Cystotomy; D005260:Female; D006115:Greece / Q000453:epidemiology; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D053244:Osteoprotegerin / Q000378:metabolism*; D011379:Prognosis; D015996:Survival Rate; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality
chemical_list: D014408:Biomarkers, Tumor; D053244:Osteoprotegerin; D053221:TNF-Related Apoptosis-Inducing Ligand; C506030:TNFRSF11B protein, human; C505653:TNFSF10 protein, human