EZH2 overexpression in primary gastrointestinal diffuse large B cell lymphoma and its association with the clinicopathological features

Publication date: Available online 22 April 2017
Source:Human Pathology
Author(s): Yang Liu, Kangjie Yu, Mingyang Li, Kaixuan Zeng, Jie Wei, Xia Li, Yixiong Liu, Danhui Zhao, Linni Fan, Zhou Yu, Yingmei Wang, Zengshan Li, Wei Zhang, Qingxian Bai, Qingguo Yan, Ying Guo, Zhe Wang, Shuangping Guo
Gastrointestinal diffuse large B cell lymphoma (GI DLBCL) is the most common gastrointestinal lymphoma, Enhancer of zeste homolog 2 (EZH2) have been implicated in the pathogenesis of several cancers. However, EZH2 has not been studied in GI DLBCL. Thus, we investigated EZH2 expression and EZH2 Y641 mutation in 100 GI DLBCL specimens by immunohistochemistry and sequencing. In addition, trimethylated H3K27 (H3K27me3), BCL2, c-MYC, and Ki-67 expression and Helicobacter pylori infection were detected, and BCL2 and c-MYC gene translocation were assessed. EZH2 was overexpressed in 50% of cases. EZH2 overexpression was significantly associated with higher stage(P=0.014), higher International Prognostic Index score(P=0.003), reduced overall survival rate(P=0.030), and H3K27me3(P=0.001)and c-MYC expression(P=0.008). We detected EZH2 mutations in 1/33 (3.0%) DLBCL with a germinal center immunophenotype (GCB-DLBCL).The frequency of EZH2 Y641 mutation with GI DLBCL was significantly lower than that of patients with DLBCL without gastrointestinal features (P =0.022). BCL2 and c-MYC translocation was detected in 6.5% and 5.1% of cases, respectively. BCL2 translocation was detected exclusively in the germinal center B cell–like subtype. Chronic gastroenteritis was present in all cases and 36.4% of gastric DLBCL cases had H. pylori infection. The data indicate that primary GI DLBCL is closely related with chronic inflammation and has a low frequency of molecular abnormality, and EZH2 overexpression is significantly associated with inferior outcome in patients with primary GI DLBCL, evaluating EZH2 expression has therapeutic implications.



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