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 language | English |
|---|---|
| Pages (from-to) | 203-11 |
| Number of pages | 9 |
| Journal | International journal of radiation oncology, biology, physics |
| Volume | 75 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Sep 2009 |
Cite this
}
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 journal › Article › Academic › peer-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 -