Virchows Archiv

, Volume 463, Issue 5, pp 697–711 | Cite as

In aggressive variants of non-Hodgkin lymphomas, Ezh2 is strongly expressed and polycomb repressive complex PRC1.4 dominates over PRC1.2

  • Lamia Abd Al Kader
  • Takashi OkaEmail author
  • Katsuyoshi Takata
  • Xu Sun
  • Hiaki Sato
  • Ichiro Murakami
  • Tomohiro Toji
  • Akihiro Manabe
  • Hiroshi Kimura
  • Tadashi Yoshino
Original Article


Polycomb group (PcG) proteins are important for the regulation of hematopoiesis by regulating chromatin compaction and silencing genes related to differentiation and cell cycle. Overexpression of enhancer of zeste homologue 2 (Ezh2) and Bmi-1/PCGF4 has been implicated in solid organ cancers, while Mel-18/PCGF2 has been reported as a tumor suppressor. Detailed expression profiles of PcG proteins and their diagnostic significance in malignant lymphomas are still unknown. In this study, we analyzed the expression levels of Ezh2, Bmi-1, Mel-18, and Ki67 in 197 Hodgkin’s and non-Hodgkin’s lymphoma patient samples and in lymphoma cell lines using immunohistochemistry, fluorescent immunocytochemistry, and Western blotting. Immunohistochemical staining showed that Ezh2 expression was significantly increased in aggressive compared to indolent subtypes of B cell neoplasms (P = 0.000–0.030), while no significant differences in Bmi-1 expression were found between these subtypes. Compared to the normal counterpart, T cell lymphomas showed significant overexpression of Bmi-1 (P = 0.011) and Ezh2 (P = 0.000). The Ki67 labeling index showed a positive correlation with Ezh2 expression in B cell lymphomas (correlation coefficient (Co) = 0.983, P = 0.000) and T/NK cell lymphomas (Co = 0.629, P = 0.000). Fluorescent immunohistochemical staining showed coexpression of Ezh2 and Ki67 in the same tumor cells, indicating that Ezh2 expression correlates with cell proliferation. Both B and T/NK cell neoplasms showed low expression of Mel-18 and high expression of both Bmi-1 and Ezh2. In conclusion, in aggressive lymphoma variants, Ezh2 is strongly expressed and polycomb repressive complex PRC1.4 dominates over PRC1.2. Coexpression of Bmi-1 and Ezh2 is a characteristic of aggressive lymphomas. Ezh2 correlates with the proliferation and aggressive nature of non-Hodgkin’s lymphomas.


Ezh2 Bmi-1 Mel-18 Malignant lymphoma PRC1.2 PRC1.4 



The authors gratefully acknowledge Drs. M. Maeda (Institute for Virus Research, Kyoto University, Kyoto, Japan), M.J. Robertson (Indiana University School of Medicine, Indianapolis, IN, USA), H. Oono (Kyoto University Medical School, Kyoto, Japan), and Y. Matsuo (Fujisaki Cell Centre, Hayashibara Biochemical Labs, Inc., Okayama, Japan) and RIKEN BioResource Centre (Tsukuba, Japan) for kindly providing the cell lines and also acknowledge Dr. A.P. Otte (University of Amsterdam, Netherlands) for providing anti-Ezh2 antibody. We also thank Mr. H. Okamoto, Mr. K. Isomoto, Ms. H. Nakamura, Ms. M. Bando, Ms. M. Shiotani, and Dr. T. Abdelkader (Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan) for the technical support. This work was supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan (T.O.) (#22590312).

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Lamia Abd Al Kader
    • 1
    • 5
  • Takashi Oka
    • 1
    Email author
  • Katsuyoshi Takata
    • 1
  • Xu Sun
    • 6
  • Hiaki Sato
    • 2
  • Ichiro Murakami
    • 1
    • 3
  • Tomohiro Toji
    • 1
  • Akihiro Manabe
    • 1
  • Hiroshi Kimura
    • 4
  • Tadashi Yoshino
    • 1
  1. 1.Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayama UniversityOkayamaJapan
  2. 2.Department of Medical Technology, Graduate School of Health SciencesOkayama UniversityOkayamaJapan
  3. 3.Department of Molecular PathologyTottori University Medical SchoolTottoriJapan
  4. 4.Nuclear Dynamics Group, Graduate School of Frontier ScienceOsaka UniversityOsakaJapan
  5. 5.Department of Pathology, Faculty of MedicineMansoura UniversityMansouraEgypt
  6. 6.Department of PathologyFirst Affiliated Hospital of Dalian Medical UniversityDalianChina

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