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
International Journal of Radiation Oncology, Biology, Physics 2009 September 1, 75 (1): 203-11

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.

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