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The role of the polycomb repressive complex pathway in T and NK cell lymphoma: biological and prognostic implications

Tumor Biology volume 37, pages 2037–2047 (2016)Cite this article

Abstract

Polycomb repressive complex 2 (PRC2; formed by EZH2, SUZ12, and EED protein subunits) and PRC1 (BMI1 protein) induce gene silencing through histone modification, primarily H3K27me3, and deregulation of PRC pathways leads to tumorigenesis. In the present study, activation of PRC2, H3K27me3, and BMI1 was investigated by immunohistochemistry in 175 cases of T and natural killer (NK) cell lymphoma. Activation of PRC proteins was analyzed according to c-MYC activation, Epstein-Barr virus (EBV) infection, CD30 activation, and survival. Among all T and NK cell lymphomas, high expression rates of 54.7 % for EZH2, 33.3 % for SUZ12, 85.7 % for EED, 40.5 % for H3K27me3, and 30.9 % for BMI1 were discovered. Activation of PRC2, H3K27me3, and BMI1 showed positive correlations (P < 0.05). Activation of c-MYC was associated with activation of SUZ12 and triple coactivation of all PRC2 protein subunits (EZH2high/SUZ12high/EEDhigh) (P < 0.05). In EBV-positive tumors, activation of EZH2 and H3K27me3 showed greater association (P < 0.05). H3K27me3 and BMI1 showed a negative association in tumors expressing CD30 (P < 0.05). With respect to survival, BMI1 activation was independently associated with poor prognosis in T and NK cell lymphomas (P = 0.002). In conclusion, T and NK cell lymphomas were associated with activation of PRC pathway markers, for which c-MYC activation and EBV infection could be suggested as possible causes. PRC pathway markers may be potential therapeutic targets and prognostic markers in T and NK cell lymphoma.

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Acknowledgments

This work was supported by grant no. 2014–01 from the Korean Medical Women’s Association.

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Author notes

  1. Soo Hee Kim

    Present address: Anatomic Pathology Reference Lab, Seegene Medical Foundation, Seoul, Korea

Authors and Affiliations

  1. Department of Pathology, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea

    Soo Hee Kim, Woo Ick Yang & Sun Och Yoon

  2. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea

    Yoo Hong Min

  3. Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

    Soo Hee Kim & Young Hyeh Ko

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Correspondence to Sun Och Yoon.

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ESM 1

Polycomb complex proteins and H3k27me3 expression in overall NK and T cell lymphoma (DOCX 22 kb)

ESM 2

The overall survival rate according to subtype of T or NK cell lymphomas using Kaplan-Meier plot (P = 0.264) (GIF 31 kb)

High resolution image (TIFF 637 kb)

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Kim, S.H., Yang, W.I., Min, Y.H. et al. The role of the polycomb repressive complex pathway in T and NK cell lymphoma: biological and prognostic implications. Tumor Biol. 37, 2037–2047 (2016). https://doi.org/10.1007/s13277-015-3977-y

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  • DOI: https://doi.org/10.1007/s13277-015-3977-y

Keywords

  • Polycomb repressive complex
  • Trimethylation of lysine 27 of histone H3
  • H3K27me3
  • c-MYC protein
  • Epstein-Barr virus
  • Lymphoma
  • T and NK cell