Diffuse large B-cell lymphoma with histone H3 trimethylation at lysine 27: another poor prognostic phenotype independent of c-Myc/Bcl2 coexpression

作者：Oh Eun Ji; Yang Woo Ick; Cheong June Won; Choi Sung eun; Yoon Sun Och^*

来源：Human Pathology, 2014, 45(10): 2043-2050.

DOI：10.1016/j.humpath.2014.07.002

• Lymphoma, large B-cel, diffuse
• Histone H3 trimethylation at lysine 27
• c-Myc
• Bcl2
• Prognosis

Deregulation of histone H3 trimethylation at lysine 27 (H3K27me3) via aberration of the histone methyltransferase, enhancer of zeste homologue 2 (EZH2), is suggested to play a critical role in cancers including hematologic malignancies. In the present study, implications of H3K27me3 were investigated in diffuse large B-cell lymphoma (DLBCL) with respect to clinicopathological factors, especially in association with c-Myc/Bcl2 coexpression and germinal center B-like (GCB) or non-GCB subtype. By immunohistochemistry, a high level of H3K27me3 was observed in approximately one-third (35.3%, 79/224) of DLBCL cases, and this subset of cases was related to poor performance status (Eastern Cooperative Oncology Group scores >= 2) (P = .013), elevated lactate dehydrogenase level (P = .001), and a higher international prognostic index risk group (scores >= 3) (P = .005). H3K27me3 level was significantly correlated with EZH2 expression (P = .004) and c-Myc protein expression (P = .003) but not correlated with c-Myc/Bcl2 coexpression or with GCB or non-GCB subtype. A high level of H3K27me3 was related to an inferior overall survival (P = .006) and was shown to be an independent prognostic factor for overall survival along with the higher international prognostic index risk group and c-Myc/Bcl2 coexpression. In conclusion, H3K27me3 was related to EZH2 and c-Myc expression, suggesting formation of a MYC-EZH2-H3K27me3 loop in a subgroup of DLBCL cases. H3K27me3 was associated with poor patient outcome and revealed as an independent predictor for overall survival of DLBCL patients. H3K27me3 in DLBCL may be another high-risk phenotype independent of the phenotype of c-Myc/Bcl2 coexpression or other known poor prognostic subgroups.

• 出版日期2014-10