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The prognostic value of TRAIL and its death receptors in cervical cancer
John H Maduro1, Maartje G Noordhuis, Klaske A ten Hoor
1Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
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.
Insights
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptors (DR4, DR5) and TRAIL are common in cervical cancer. TRAIL absence predicts better radiotherapy response, but these markers lack prognostic value for survival.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Preclinical studies suggest synergy between irradiation and recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL) in inducing apoptosis.
- TRAIL death receptors (DR4, DR5) are potential therapeutic targets due to their role in apoptosis signaling pathways.
Purpose of the Study:
- To investigate the expression of DR4, DR5, and TRAIL in cervical cancer.
- To evaluate the predictive and prognostic significance of DR4, DR5, and TRAIL in cervical cancer patients.
Main Methods:
- Tumor tissue microarrays from 645 cervical cancer patients were analyzed.
- Immunohistochemistry was employed to assess the expression of DR4, DR5, and TRAIL.
- Expression levels were correlated with clinicopathological variables, radiotherapy response, and disease-specific survival.
Main Results:
- High prevalence of cytoplasmic DR4 (99%), DR5 (88%), and TRAIL (81%) expression was observed in cervical tumors.
- TRAIL-positive tumors showed a lower pathological complete response rate to radiotherapy compared to TRAIL-negative tumors (66.3% vs. 79.0%).
- Multivariate analysis indicated TRAIL expression was not prognostic for disease-specific survival (OR: 2.09, p <= 0.05).
Conclusions:
- DR4, DR5, and TRAIL are frequently expressed in the cytoplasm of cervical cancer cells.
- Absence of TRAIL expression is associated with an improved pathological complete response to radiotherapy.
- DR4, DR5, and TRAIL expression did not demonstrate prognostic value for disease-specific survival in this cohort.
