Divergent Effects of EZH1 and EZH2 Protein Expression on the Prognosis of Patients with T-Cell Lymphomas
Franziska Lea Schümann,
Elisabeth Groß,
Marcus Bauer,
Christian Rohde,
Sarah Sandmann,
Denis Terziev,
Lutz P. Müller,
Guido Posern,
Andreas Wienke,
Falko Fend,
Martin-Leo Hansmann,
Wolfram Klapper,
Andreas Rosenwald,
Harald Stein,
Martin Dugas,
Carsten Müller-Tidow,
Claudia Wickenhauser,
Mascha Binder,
Thomas Weber
Affiliations
Franziska Lea Schümann
Department of Internal Medicine IV, Hematology and Oncology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, 06120 Halle, Germany
Elisabeth Groß
Department of Internal Medicine IV, Hematology and Oncology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, 06120 Halle, Germany
Marcus Bauer
Institute of Pathology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, 06112 Halle, Germany
Christian Rohde
Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, 69120 Heidelberg, Germany
Sarah Sandmann
Institute of Medical Informatics, University of Münster, 48149 Münster, Germany
Denis Terziev
Department of Internal Medicine IV, Hematology and Oncology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, 06120 Halle, Germany
Lutz P. Müller
Department of Internal Medicine IV, Hematology and Oncology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, 06120 Halle, Germany
Guido Posern
Institute for Physiological Chemistry, Medical Faculty, Martin Luther University Halle-Wittenberg, 06114 Halle, Germany
Andreas Wienke
Institute of Medical Epidemiology, Biometrics and Informatics, Martin-Luther-University Halle-Wittenberg, 06112 Halle, Germany
Falko Fend
Institute of Pathology, University Hospital Tübingen, 72076 Tübingen, Germany
Martin-Leo Hansmann
Institute of Pathology and Molecular Pathology, Helios University Hospital Wuppertal, 42283 Wuppertal, Germany
Wolfram Klapper
Department of Pathology, Hematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein, Christian-Albrechts-University, 24105 Kiel, Germany
Andreas Rosenwald
Institute of Pathology, University Würzburg, 97080 Würzburg, Germany
Harald Stein
Pathodiagnostik Berlin, 12099 Berlin, Germany
Martin Dugas
Institute for Medical Informatics, University Hospital Heidelberg, 69120 Heidelberg, Germany
Carsten Müller-Tidow
Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, 69120 Heidelberg, Germany
Claudia Wickenhauser
Institute of Pathology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, 06112 Halle, Germany
Mascha Binder
Department of Internal Medicine IV, Hematology and Oncology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, 06120 Halle, Germany
Thomas Weber
Department of Internal Medicine IV, Hematology and Oncology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, 06120 Halle, Germany
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.
