Death receptor expression is associated with poor response to chemotherapy and shorter survival in metastatic ovarian carcinoma

BACKGROUND: Death receptors mediate both apoptosis and survival in cancer cells. The authors analyzed death receptor expression in metastatic ovarian carcinoma. METHODS: Viable tumor cells in ovarian carcinoma effusions (n = 95) were analyzed for DR4, DR5, Fas, TNFR1, and TNFR2 expression using flow cytometry. Results were analyzed for association with clinicopathologic parameters, chemotherapy response, and survival. RESULTS: DR4, DR5, and Fas were expressed by the majority of specimens, with less frequent expression of TNFR1 and TNFR2. DR4 (P = .005) and TNFR2 (P = .041) expression was higher in FIGO stage IV compared with stage III tumors. Effusions from patients who responded poorly to chemotherapy administered at disease recurrence had significantly higher DR4 (P = .006), DR5 (P = .01), and Fas (P = .001) expression. In univariate survival analysis, higher DR4 expression in viable cells correlated with poor overall (P = .0352) and progression-free (P = .0411) survival. DR4 expression was found to be an independent predictor of overall (P = .008) and progression-free (P = .003) survival. CONCLUSIONS: The authors have presented the first evidence of death receptor coexpression in ovarian carcinoma effusions. The association of death receptor expression in effusions with advanced stage, poor response to chemotherapy, and shorter survival suggests that these molecules are linked to an aggressive clinical course in metastatic ovarian carcinoma.