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.

doi:10.1016/j.ijrobp.2009.03.071

« Previous Next »International Journal of Radiation Oncology * Biology * Physics
Volume 75, Issue 1 , Pages 203-211, 1 September 2009

The Prognostic Value of TRAIL and its Death Receptors in Cervical Cancer

John H. Maduro, M.D.
- Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Reprint requests to: J. H. Maduro, M.D., Department of Radiation Oncology, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. Tel: (+31) 50-3619382; Fax: (+31) 50-3611692
Maartje G. Noordhuis, B.Sc.
- Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Klaske A. ten Hoor
- Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Elisabeth Pras, M.D., Ph.D.
- Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Henriette J.G. Arts, M.D., Ph.D.
- Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Jasper J.H. Eijsink, M.D.
- Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Harry Hollema, M.D., Ph.D.
- Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Constantijne H. Mom, M.D., Ph.D.
- Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Steven de Jong, Ph.D.
- Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Elisabeth G.E. de Vries, M.D., Ph.D.
- Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Geertruida H. de Bock, Ph.D.
- Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Ate G.J. van der Zee, M.D., Ph.D.
- Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Received 7 November 2008; received in revised form 1 March 2009; accepted 13 March 2009.

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.

Cervical cancer, TRAIL, Death receptors, Radiotherapy, Immunohistochemistry