Expression of COX-2 on Reed-Sternberg cells is an independent unfavorable prognostic factor in Hodgkin lymphoma treated with ABVD

Cyclooxygenase 2 (COX-2) is an inflammatory enzyme involved in the pathogenesis and prognosis of several malignancies. In the present study, we investigated the prognostic value of COX-2 expression in a large (N = 242), uniformly treated Hodgkin lymphoma (HL) population from the Spanish Network of HL using tissue microarrays. Univariate and multivariate analysis was done, including comparing the most recognized clinical variables: the early- and advanced-stage subgroups. COX-2 was expressed on Reed-Sternberg cells in 37% of patients. There were no differences in the distribution of clinical variables according to COX-2 expression. With a median follow-up time of 58 months, PFS at 5 years was 60% and 79% for COX-2(+) and COX-2(-) patients, respectively (P = .003). The overall survival was 73% and 91%, respectively (P < .001). The major impact on prognosis was observed in the early AA stage (I-II) group. In fact, in these low-risk groups the expression of COX-2 defined a group with significantly worse progression-free and overall survival. In conclusion, COX-2 was expressed on Reed-Sternberg cells in one-third of HL patients and was a major independent, unfavorable prognostic factor in early-stage HL. We conclude that COX-2 may be a major prognostic variable in HL and a potential therapeutic target. (Blood. 2012; 119(25):6072-6079)