Kim Soo Hee, Yang Woo Ick, Min Yoo Hong, Ko Young Hyeh, Yoon Sun Och
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.
Tumour Biol. 2016 Feb;37(2):2037-47. doi: 10.1007/s13277-015-3977-y. Epub 2015 Sep 4.
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.
多梳抑制复合物2（PRC2；由EZH2、SUZ12和EED蛋白亚基组成）和PRC1（BMI1蛋白）通过组蛋白修饰（主要是H3K27me3）诱导基因沉默，PRC通路失调会导致肿瘤发生。在本研究中，通过免疫组织化学对175例T细胞和自然杀伤（NK）细胞淋巴瘤病例中的PRC2、H3K27me3和BMI1的激活情况进行了研究。根据c-MYC激活、爱泼斯坦-巴尔病毒（EBV）感染、CD30激活和生存率对PRC蛋白的激活情况进行了分析。在所有T细胞和NK细胞淋巴瘤中，发现EZH2的高表达率为54.7%，SUZ12为33.3%，EED为85.7%，H3K27me3为40.5%，BMI1为30.9%。PRC2、H3K27me3和BMI1的激活呈正相关（P<0.05）。c-MYC的激活与SUZ12的激活以及所有PRC2蛋白亚基的三联激活（EZH2(高)/SUZ12(高)/EED(高)）相关（P<0.05）。在EBV阳性肿瘤中，EZH2和H3K27me3的激活表现出更强的相关性（P<0.05）。在表达CD30的肿瘤中，H3K27me3和BMI1呈负相关（P<0.05）。关于生存率，BMI1的激活与T细胞和NK细胞淋巴瘤的不良预后独立相关（P=0.002）。总之，T细胞和NK细胞淋巴瘤与PRC通路标志物的激活相关，其中c-MYC激活和EBV感染可能是其潜在原因。PRC通路标志物可能是T细胞和NK细胞淋巴瘤的潜在治疗靶点和预后标志物。
