title: Prognostic value of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and TRAIL receptors in renal cell cancer.
abstract: OBJECTIVE
  The death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors (TRAIL-R) are involved in immune surveillance and tumor development. Here, we studied a possible association between the expression of TRAIL/TRAIL-Rs and the prognosis in patients with renal cell carcinomas (RCC).
  
  
  METHODS
  A tissue microarray containing RCC tumor tissue samples and corresponding normal tissue samples from 838 patients was generated. Expression of TRAIL and TRAIL-Rs was examined by immunohistochemistry and the effect of TRAIL and TRAIL-R expression on disease-specific survival was assessed.
  
  
  RESULTS
  High TRAIL-R2 expression levels were associated with high-grade RCCs (P < 0.001) and correlated negatively with disease-specific survival (P = 0.01). Similarly, high TRAIL expression was associated with a shorter disease-specific survival (P = 0.01). In contrast, low TRAIL-R4 expression was associated with high-stage RCCs (P < 0.001) as well as with the incidence of distant metastasis (P = 0.03) and correlated negatively with disease-specific survival (P = 0.02). In patients without distant metastasis, multivariate Cox regression analyses revealed that TRAIL-R2 and TRAIL are independent prognostic factors for cancer-specific survival (in addition to tumor extent, regional lymph node metastasis, grade of malignancy, and type of surgery).
  
  
  CONCLUSIONS
  High TRAIL-R2, high TRAIL, and low TRAIL-R4 expression levels are associated with a worse disease-specific survival in patients with RCCs. Therefore, the assessment of TRAIL/TRAIL-R expression offers valuable prognostic information that could be used to select patients for adjuvant therapy studies. Moreover, our findings are of relevance for a potential experimental therapeutic administration of TRAIL-R agonists in patients with RCCs.
authors.affiliation: Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Macher-Goeppinger
authors.forename: Sebastian
authors.initials: S
authors.lastname: Aulmann
authors.forename: Katrin E
authors.initials: KE
authors.lastname: Tagscherer
authors.forename: Nina
authors.initials: N
authors.lastname: Wagener
authors.forename: Axel
authors.initials: A
authors.lastname: Haferkamp
authors.forename: Roland
authors.initials: R
authors.lastname: Penzel
authors.forename: Antje
authors.initials: A
authors.lastname: Brauckhoff
authors.forename: Markus
authors.initials: M
authors.lastname: Hohenfellner
authors.forename: Jaromir
authors.initials: J
authors.lastname: Sykora
authors.forename: Henning
authors.initials: H
authors.lastname: Walczak
authors.forename: Bin T
authors.initials: BT
authors.lastname: Teh
authors.forename: Frank
authors.initials: F
authors.lastname: Autschbach
authors.forename: Esther
authors.initials: E
authors.lastname: Herpel
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.forename: Wilfried
authors.initials: W
authors.lastname: Roth
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand