title: Strong KDM4B and KDM4D Expression Associates with Radioresistance and Aggressive Phenotype in Classical Hodgkin Lymphoma.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  KDM4B and KDM4D expression may associate with an aggressive subtype of classical Hodgkin lymphoma and be linked with radioresistance.
authors.affiliation: Department of Oncology and Radiotherapy, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Hamid
authors.initials: H
authors.lastname: Bur
authors.affiliation: Department of Pathology, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Kirsi-Maria
authors.initials: KM
authors.lastname: Haapasaari
authors.affiliation: Department of Oncology and Radiotherapy, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Taina
authors.initials: T
authors.lastname: Turpeenniemi-Hujanen
authors.affiliation: Department of Oncology and Radiotherapy, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Kuittinen
authors.affiliation: Department of Oncology, Cancer Center of Eastern Finland, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Auvinen
authors.affiliation: Department of Oncology, Cancer Center of Eastern Finland, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Katja
authors.initials: K
authors.lastname: Marin
authors.affiliation: Department of Pathology and Forensic Medicine, University of Eastern Finland, Cancer Center of Eastern Finland, Kuopio, Finland.
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
authors.affiliation: Department of Oncology and Radiotherapy, Oulu University Hospital and University of Oulu, Oulu, Finland peeter.karihtala@oulu.fi.
authors.forename: Peeter
authors.initials: P
authors.lastname: Karihtala
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001761:Bleomycin / Q000008:administration & dosage; D003593:Cytoplasm / Q000378:metabolism; D003606:Dacarbazine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D044127:Epigenesis, Genetic; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007150:Immunohistochemistry; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D014747:Vinblastine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D001761:Bleomycin; D014747:Vinblastine; D003606:Dacarbazine; D004317:Doxorubicin; D056484:Jumonji Domain-Containing Histone Demethylases; C523637:KDM4B protein, human; C521694:KDM4D protein, human
keywords: Hodgkin lymphoma; KDM4B; KDM4D; radioresistance