The role of the polycomb repressive complex pathway in T and NK cell lymphoma: biological and prognostic implications.
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 (EZH2(high)/SUZ12(high)/EED(high)) (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.
Department of Pathology, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.|Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Anatomic Pathology Reference Lab, Seegene Medical Foundation, Seoul, Korea.
Soo Hee
SH
Kim
Department of Pathology, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
Woo Ick
WI
Yang
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Yoo Hong
YH
Min
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Young Hyeh
YH
Ko
Department of Pathology, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea. soyoon@yuhs.ac.
Sun Och
SO
Yoon
D000328:Adult; D000368:Aged; D019175:DNA Methylation / Q000502:physiology; D020031:Epstein-Barr Virus Infections / Q000150:complications; D005260:Female; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D054391:Lymphoma, Extranodal NK-T-Cell / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D016399:Lymphoma, T-Cell / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D046888:Tissue Array Analysis
C069077:BMI1 protein, human; D006657:Histones; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D063151:Polycomb Repressive Complex 2; D063150:Polycomb Repressive Complex 1
Epstein-Barr virus; H3K27me3; Lymphoma; Polycomb repressive complex; T and NK cell; Trimethylation of lysine 27 of histone H3; c-MYC protein