Strong KDM4B and KDM4D Expression Associates with Radioresistance and Aggressive Phenotype in Classical Hodgkin Lymphoma

Background: Epigenetic regulators, including Jumonji domain 2 (JMJD2/KDM4) proteins are involved in post-translational modification of histone demethylation and have a major role in carcinogenesis of many solid tumors. Materials and Methods: We assessed immunohistochemically the expression of lysine (K)-specific demethylase 4 (KDM4) A, KDM4B and KDM4D in tumors from 91 patients of adriamycin, bleomycin, vinblastine, darcabazine (ABVD)-treated classical Hodgkin lymphoma. Results: Strong cytoplasmic KDM4B expression in the reactive cellular infiltrate and also in Reed-Sternberg (RS) cells predicted poor relapse-free survival (RFS) (p=0.020 and p=0.022, respectively) in patients with limited-stage disease. Strong KDM4B expression in RS cells was also related to B-symptoms (p=0.007) and advanced stage (p=0.024). Strong KDM4D expression in the cytoplasm of RS cells was also associated with poor RFS in limited-stage patients RFS (p=0.043) and, most significantly, in patients receiving involved-field radiotherapy (p=0.007). Conclusion: KDM4B and KDM4D expression may associate with an aggressive subtype of classical Hodgkin lymphoma and be linked with radioresistance.