The prognostic value of TRAIL and its death receptors in cervical cancer.
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.
Maduro
John H
JH
Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Noordhuis
Maartje G
MG
ten Hoor
Klaske A
KA
Pras
Elisabeth
E
Arts
Henriette J G
HJ
Eijsink
Jasper J H
JJ
Hollema
Harry
H
Mom
Constantijne H
CH
de Jong
Steven
S
de Vries
Elisabeth G E
EG
de Bock
Geertruida H
GH
van der Zee
Ate G J
AG
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
D009363:Neoplasm Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D016190:Carboplatin; D005472:Fluorouracil