Prognostic Value of Histone Modifying Enzyme EZH2 in RCHOP-Treated Diffuse Large B-Cell Lymphoma and High Grade B-Cell Lymphoma

被引:0
作者
Petronilho, Sara [1 ,2 ]
Sequeira, Jose Pedro [2 ]
Paulino, Sofia [1 ,2 ]
Lopes, Paula [1 ,2 ]
Lisboa, Susana [3 ]
Chacim, Sergio [2 ,4 ]
Lobo, Joao [1 ,2 ,3 ,5 ]
Teixeira, Manuel [5 ]
Jeronimo, Carmen [2 ,5 ]
Henrique, Rui [1 ,2 ,5 ]
机构
[1] Portuguese Oncol Inst Porto IPO Porto, Dept Pathol, R Dr Antonio Bernardino de Almeida, P-4200072 Porto, Portugal
[2] Portuguese Oncol Inst Porto IPO Porto, Canc Biol & Epigenet Grp, Res Ctr IPO Porto CI IPOP, RISE CIIPOP Hlth Res Network,Porto Comprehens Can, R Dr Antonio Bernardino de Almeida, P-4200072 Porto, Portugal
[3] Portuguese Oncol Inst Porto IPO Porto, Dept Genet, R Dr Antonio Bernardino de Almeida, P-4200072 Porto, Portugal
[4] Portuguese Oncol Inst Porto IPO Porto, Dept Hematol, R Dr Antonio Bernardino de Almeida, P-4200072 Porto, Portugal
[5] Univ Porto ICBAS, Inst Biomed Sci Abel Salazar, Dept Pathol & Mol Immunol, Rua Jorge Viterbo Ferreira 228, P-4050513 Porto, Portugal
关键词
DLBCL; HGBCL; RCHOP; epigenetics; histones; prognostic; EZH2; SOMATIC MUTATIONS; EXPRESSION; RITUXIMAB; CYCLOPHOSPHAMIDE; COEXPRESSION; VINCRISTINE; DOXORUBICIN; SURVIVAL; PROTEIN; MYC;
D O I
10.3390/jpm11121384
中图分类号
R19 [保健组织与事业(卫生事业管理)];
学科分类号
摘要
Background: DLBCL represent a heterogeneous group of aggressive diseases. High grade B-cell lymphomas (HGBCL) were recently individualized from DLBCL as a discrete diagnostic entity due to their worse prognosis. Currently, although most patients are successfully treated with RCHOP regimens, 1/3 will either not respond or ultimately relapse. Alterations in histone modifying enzymes have emerged as the most common alterations in DLBCL, but their role as prognostic biomarkers is controversial. We aimed to ascertain the prognostic value of EZH2 immunoexpression in RCHOP-treated DLBCL and HGBCL. Results: We performed a retrospective cohort study including 125 patients with RCHOP-treated DLBCL or HGBCL. EZH2 expression levels did not differ between diagnostic groups or between DLBCL-NOS molecular groups. We found no associations between EZH2 expression levels and outcome, including in the subgroup analysis (GC versus non-GC). Nonetheless, EZH2/BCL2 co-expression was significantly associated with worse outcome (event free survival and overall survival). Conclusion: Although EZH2 mutations are almost exclusively found in GC-DLBCL, we found similar EZH2 expression levels in both DLBCL-NOS molecular groups, suggesting non-mutational mechanisms of EZH2 deregulation. These findings suggest that the use of EZH2 antagonists might be extended to non-GC DLBCL patients with clinical benefit. EZH2/BCL2 co-expression was associated with a worse outcome.
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页数:14
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