The prognostic value of TRAIL and its death receptors in cervical cancer

John H Maduro, Maartje G Noordhuis, Klaske A ten Hoor, Elisabeth Pras, Henriette J G Arts, Jasper J H Eijsink, Harry Hollema, Constantijne H Mom, Steven de Jong, Elisabeth G E de Vries, Geertruida H de Bock, Ate G J van der Zee

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

PURPOSE: 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 AND MATERIALS: 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.

Original languageEnglish
Pages (from-to)203-11
Number of pages9
JournalInternational journal of radiation oncology, biology, physics
Volume75
Issue number1
DOIs
Publication statusPublished - 1 Sep 2009

Cite this

Maduro, J. H., Noordhuis, M. G., ten Hoor, K. A., Pras, E., Arts, H. J. G., Eijsink, J. J. H., ... van der Zee, A. G. J. (2009). The prognostic value of TRAIL and its death receptors in cervical cancer. International journal of radiation oncology, biology, physics, 75(1), 203-11. https://doi.org/10.1016/j.ijrobp.2009.03.071
Maduro, John H ; Noordhuis, Maartje G ; ten Hoor, Klaske A ; Pras, Elisabeth ; Arts, Henriette J G ; Eijsink, Jasper J H ; Hollema, Harry ; Mom, Constantijne H ; de Jong, Steven ; de Vries, Elisabeth G E ; de Bock, Geertruida H ; van der Zee, Ate G J. / The prognostic value of TRAIL and its death receptors in cervical cancer. In: International journal of radiation oncology, biology, physics. 2009 ; Vol. 75, No. 1. pp. 203-11.
@article{c5adf071079a4acd8dfc6fbf086dd521,
title = "The prognostic value of TRAIL and its death receptors in cervical cancer",
abstract = "PURPOSE: 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 AND MATERIALS: 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 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.",
keywords = "Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Apoptosis, Carboplatin/administration & dosage, Cytoplasm/chemistry, Female, Fluorouracil/administration & dosage, Humans, Immunohistochemistry, Middle Aged, Multivariate Analysis, Neoplasm Proteins/analysis, Prognosis, Radiotherapy Dosage, Receptors, TNF-Related Apoptosis-Inducing Ligand/analysis, TNF-Related Apoptosis-Inducing Ligand/analysis, Tissue Array Analysis, Uterine Cervical Neoplasms/chemistry, Young Adult",
author = "Maduro, {John H} and Noordhuis, {Maartje G} and {ten Hoor}, {Klaske A} and Elisabeth Pras and Arts, {Henriette J G} and Eijsink, {Jasper J H} and Harry Hollema and Mom, {Constantijne H} and {de Jong}, Steven and {de Vries}, {Elisabeth G E} and {de Bock}, {Geertruida H} and {van der Zee}, {Ate G J}",
year = "2009",
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language = "English",
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journal = "International Journal of Radiation Oncology Biology Physics",
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Maduro, JH, Noordhuis, MG, ten Hoor, KA, Pras, E, Arts, HJG, Eijsink, JJH, Hollema, H, Mom, CH, de Jong, S, de Vries, EGE, de Bock, GH & van der Zee, AGJ 2009, 'The prognostic value of TRAIL and its death receptors in cervical cancer' International journal of radiation oncology, biology, physics, vol. 75, no. 1, pp. 203-11. https://doi.org/10.1016/j.ijrobp.2009.03.071

The prognostic value of TRAIL and its death receptors in cervical cancer. / Maduro, John H; Noordhuis, Maartje G; ten Hoor, Klaske A; Pras, Elisabeth; Arts, Henriette J G; Eijsink, Jasper J H; Hollema, Harry; Mom, Constantijne H; de Jong, Steven; de Vries, Elisabeth G E; de Bock, Geertruida H; van der Zee, Ate G J.

In: International journal of radiation oncology, biology, physics, Vol. 75, No. 1, 01.09.2009, p. 203-11.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The prognostic value of TRAIL and its death receptors in cervical cancer

AU - Maduro, John H

AU - Noordhuis, Maartje G

AU - ten Hoor, Klaske A

AU - Pras, Elisabeth

AU - Arts, Henriette J G

AU - Eijsink, Jasper J H

AU - Hollema, Harry

AU - Mom, Constantijne H

AU - de Jong, Steven

AU - de Vries, Elisabeth G E

AU - de Bock, Geertruida H

AU - van der Zee, Ate G J

PY - 2009/9/1

Y1 - 2009/9/1

N2 - PURPOSE: 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 AND MATERIALS: 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 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.

AB - PURPOSE: 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 AND MATERIALS: 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 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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Apoptosis

KW - Carboplatin/administration & dosage

KW - Cytoplasm/chemistry

KW - Female

KW - Fluorouracil/administration & dosage

KW - Humans

KW - Immunohistochemistry

KW - Middle Aged

KW - Multivariate Analysis

KW - Neoplasm Proteins/analysis

KW - Prognosis

KW - Radiotherapy Dosage

KW - Receptors, TNF-Related Apoptosis-Inducing Ligand/analysis

KW - TNF-Related Apoptosis-Inducing Ligand/analysis

KW - Tissue Array Analysis

KW - Uterine Cervical Neoplasms/chemistry

KW - Young Adult

U2 - 10.1016/j.ijrobp.2009.03.071

DO - 10.1016/j.ijrobp.2009.03.071

M3 - Article

VL - 75

SP - 203

EP - 211

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 1

ER -