Divergent Effects of EZH1 and EZH2 Protein Expression on the Prognosis of Patients with T-Cell Lymphomas.

Autor: Schümann FL; Department of Internal Medicine IV, Hematology and Oncology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, 06120 Halle, Germany., Groß E; Department of Internal Medicine IV, Hematology and Oncology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, 06120 Halle, Germany., Bauer M; Institute of Pathology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, 06112 Halle, Germany., Rohde C; Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, 69120 Heidelberg, Germany., Sandmann S; Institute of Medical Informatics, University of Münster, 48149 Münster, Germany., Terziev D; Department of Internal Medicine IV, Hematology and Oncology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, 06120 Halle, Germany., Müller LP; Department of Internal Medicine IV, Hematology and Oncology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, 06120 Halle, Germany., Posern G; Institute for Physiological Chemistry, Medical Faculty, Martin Luther University Halle-Wittenberg, 06114 Halle, Germany., Wienke A; Institute of Medical Epidemiology, Biometrics and Informatics, Martin-Luther-University Halle-Wittenberg, 06112 Halle, Germany., Fend F; Institute of Pathology, University Hospital Tübingen, 72076 Tübingen, Germany., Hansmann ML; Institute of Pathology and Molecular Pathology, Helios University Hospital Wuppertal, 42283 Wuppertal, Germany., Klapper W; Department of Pathology, Hematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein, Christian-Albrechts-University, 24105 Kiel, Germany., Rosenwald A; Institute of Pathology, University Würzburg, 97080 Würzburg, Germany., Stein H; Pathodiagnostik Berlin, 12099 Berlin, Germany., Dugas M; Institute for Medical Informatics, University Hospital Heidelberg, 69120 Heidelberg, Germany., Müller-Tidow C; Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, 69120 Heidelberg, Germany., Wickenhauser C; Institute of Pathology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, 06112 Halle, Germany., Binder M; Department of Internal Medicine IV, Hematology and Oncology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, 06120 Halle, Germany., Weber T; Department of Internal Medicine IV, Hematology and Oncology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, 06120 Halle, Germany.
Jazyk: angličtina
Zdroj: Biomedicines [Biomedicines] 2021 Dec 05; Vol. 9 (12). Date of Electronic Publication: 2021 Dec 05.
DOI: 10.3390/biomedicines9121842
Abstrakt: T-cell lymphomas are highly heterogeneous and their prognosis is poor under the currently available therapies. Enhancers of zeste homologue 1 and 2 (EZH1/2) are histone H3 lysine-27 trimethyltransferases (H3K27me3). Despite the rapid development of new drugs inhibiting EZH2 and/or EZH1, the molecular interplay of these proteins and the impact on disease progression and prognosis of patients with T-cell lymphomas remains insufficiently understood. In this study, EZH1/2 mutation status was evaluated in 33 monomorphic epitheliotropic intestinal T-cell lymphomas by next generation sequencing and EZH1/2 and H3K27me3 protein expression levels were detected by immunohistochemistry in 46 T-cell lymphomas. Correlations with clinicopathologic features were analyzed and survival curves generated. No EZH1 mutations and one (3%) EZH2 missense mutation were identified. In univariable analysis, high EZH1 expression was associated with an improved overall survival (OS) and progression-free survival (PFS) whereas high EZH2 and H3K27me3 expression were associated with poorer OS and PFS. Multivariable analysis revealed EZH1 (hazard ratio (HR) = 0.183; 95% confidence interval (CI): 0.044-0.767; p = 0.020;) and EZH2 (HR = 8.245; 95% CI: 1.898-35.826; p = 0.005) to be independent, divergent prognostic markers for OS. In conclusion, EZH1/2 protein expression had opposing effects on the prognosis of T-cell lymphoma patients.
Databáze: MEDLINE