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

Anticancer Res. 2016 Sep;36(9):4677-83. doi: 10.21873/anticanres.11020.

Abstract

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.

Keywords: Hodgkin lymphoma; KDM4B; KDM4D; radioresistance.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bleomycin / administration & dosage
  • Cytoplasm / metabolism
  • Dacarbazine / administration & dosage
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Epigenesis, Genetic
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Hodgkin Disease / drug therapy
  • Hodgkin Disease / metabolism*
  • Hodgkin Disease / pathology
  • Hodgkin Disease / radiotherapy*
  • Humans
  • Immunohistochemistry
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Phenotype
  • Protein Processing, Post-Translational
  • Vinblastine / administration & dosage
  • Young Adult

Substances

  • Bleomycin
  • Vinblastine
  • Dacarbazine
  • Doxorubicin
  • Jumonji Domain-Containing Histone Demethylases
  • KDM4B protein, human
  • KDM4D protein, human