title: The prognostic value of TRAIL and its death receptors in cervical cancer.
abstract: OBJECTIVE
  Preclinical data indicate a synergistic effect on apoptosis between irradiation and recombinant human (rh) tumor necrosis factor-related apoptosis inducing ligand (TRAIL), making the TRAIL death receptors (DR) interesting drug targets. The aim of our study was to analyze the expression of DR4, DR5, and TRAIL in cervical cancer and to determine their predictive and prognostic value.
  
  
  METHODS
  Tissue microarrays were constructed from tumors of 645 cervical cancer patients treated with surgery and/or (chemo-)radiation between 1980 and 2004. DR4, DR5, and TRAIL expression in the tumor was studied by immunohistochemistry and correlated to clinicopathological variables, response to radiotherapy, and disease-specific survival.
  
  
  RESULTS
  Cytoplasmatic DR4, DR5, and TRAIL immunostaining were observed in cervical tumors from 99%, 88%, and 81% of the patients, respectively. In patients treated primarily with radiotherapy, TRAIL-positive tumors less frequently obtained a pathological complete response than TRAIL-negative tumors (66.3% vs. 79.0 %; in multivariate analysis: odds ratio: 2.09, p </=0.05). DR4, DR5, and TRAIL expression were not prognostic for disease-specific survival.
  
  
  CONCLUSIONS
  Immunostaining for DR4, DR5, and TRAIL is frequently observed in the cytoplasm of tumor cells in cervical cancer patients. Absence of TRAIL expression was associated with a higher pathological complete response rate to radiotherapy. DR4, DR5, or TRAIL were not prognostic for disease-specific survival.
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: John H
authors.initials: JH
authors.lastname: Maduro
authors.forename: Maartje G
authors.initials: MG
authors.lastname: Noordhuis
authors.forename: Klaske A
authors.initials: KA
authors.lastname: ten Hoor
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Pras
authors.forename: Henriette J G
authors.initials: HJ
authors.lastname: Arts
authors.forename: Jasper J H
authors.initials: JJ
authors.lastname: Eijsink
authors.forename: Harry
authors.initials: H
authors.lastname: Hollema
authors.forename: Constantijne H
authors.initials: CH
authors.lastname: Mom
authors.forename: Steven
authors.initials: S
authors.lastname: de Jong
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
authors.forename: Geertruida H
authors.initials: GH
authors.lastname: de Bock
authors.forename: Ate G J
authors.initials: AG
authors.lastname: van der Zee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis; D016190:Carboplatin / Q000008:administration & dosage; D003593:Cytoplasm / Q000737:chemistry*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000032:analysis*; D011379:Prognosis; D011879:Radiotherapy Dosage; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000032:analysis*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000032:analysis*; D046888:Tissue Array Analysis; D002583:Uterine Cervical Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D055815:Young Adult
chemical_list: D009363:Neoplasm Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D016190:Carboplatin; D005472:Fluorouracil