Strong Prolyl Hydroxylase Domain 1 Expression Predicts Poor Outcome in Radiotherapy-treated Patients with Classical Hodgkin's Lymphoma

Background: Hypoxia-inducible factors (HIFs) and prolyl hydroxylase domain (PHD) proteins control cellular oxygen homeostasis and a wide range of other processes. Materials and Methods: We immunohistochemically assessed the expression of HIF1 alpha, HIF2 alpha, PHD1, PHD2 and PHD3 in 115 cases of classical Hodgkin's lymphoma, all treated in the first line with doxorubicin, bleomycin, vinblastine and darcabazine (ABVD) chemotherapy. Results: In advanced-stage patients treated with involved-field radiotherapy (IFRT), nuclear HIF1 alpha expression in reactive cellular infiltrate predicted prolonged relapse-free survival (RFS) (p=0.026). Strong cytoplasmic PHD1 expression in Reed-Sternberg cells was associated with poor RFS among patients treated with IFRT and advanced-stage patients treated with ABVD and IFRT (p=0.0028 and p=0.0058, respectively). In Cox regression analysis, PHD1 was a more significant predictor of relapse (risk ratio=18.383; 95% confidence interval(CI)=1.521-222.246; p=0.022) than the International Prognostic Score. Conclusion: HIF and PHD expression appear to be novel prognostic biomarkers in classical Hodgkin's lymphoma.