DNA methylation profiling identifies two distinct subgroups in breast cancers with low hormone receptor expression, mainly associated with HER2 amplification status
Clinical Epigenetics, vol. 13, pp. 184
Abstract
BACKGROUND: Current clinical guidelines suggest that breast cancers with low hormone receptor expression (LowHR) in 1-10% of tumor cells should be regarded as hormone receptor positive. However, clinical data show that these patients have worse outcome compared to patients with hormone receptor expression above 10%. We performed DNA methylation profiling on 23 LowHR breast cancer specimens, including 13 samples with HER2 amplification and compared our results with a reference breast cancer cohort from The Cancer Genome Atlas to clarify the status for this infrequent but important patient subgroup. RESULTS: In unsupervised clustering and dimensionality reduction, breast cancers with low hormone receptor expression that lacked HER2 amplification usually clustered with triple negative breast cancer (TNBC) reference samples (8/10; "LowHR TNBC-like"). In contrast, most specimens with low hormone receptor expression and HER2 amplification grouped with hormone receptor positive cancers (11/13; "LowHR HRpos-like"). We observed highly similar DNA methylation patterns of LowHR TNBC-like samples and true TNBCs. Furthermore, the Ki67 proliferation index of LowHR TNBC-like samples and clinical outcome parameters were more similar to TNBCs and differed from LowHR HRpos-like cases. CONCLUSIONS: We here demonstrate that LowHR breast cancer comprises two epigenetically distinct groups. Our data strongly suggest that LowHR TNBC-like samples are molecularly, histologically and clinically closely related to TNBC, while LowHR HRpos-like specimens are closely related to hormone receptor positive tumors.
Authors 20
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Philipp Sebastian Jurmeister corresponding
German Cancer Research Center · LMU Klinikum · Humboldt-Universität zu Berlin · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Deutsches Konsortium für Translationale Krebsforschung · Pathologisches Institut · Freie Universität Berlin · Charité - Universitätsmedizin Berlin · Ludwig-Maximilians-Universität München
Affiliation as printed
Berlin Institute of Health, Anna-Louisa-Karsch-Straße 2, 10178, Berlin, Germany. philipp.jurmeister@med.uni-muenchen.de
German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), 69210, Heidelberg, Germany. philipp.jurmeister@med.uni-muenchen.de
Institute of Pathology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 10117, Berlin, Germany. philipp.jurmeister@med.uni-muenchen.de
Institute of Pathology, Ludwig Maximilians University Hospital Munich, Thalkirchner Str. 36, 80337, Munich, Germany. philipp.jurmeister@med.uni-muenchen.de
Berlin Institute of Health, Anna-Louisa-Karsch-Straße 2, 10178, Berlin, Germany
German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), 69210, Heidelberg, Germany
Institute of Pathology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 10117, Berlin, Germany
Institute of Pathology, Ludwig Maximilians University Hospital Munich, Thalkirchner Str. 36, 80337, Munich, Germany
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Affiliation as printed
German Breast Group, 63263, Neu-Isenburg, Germany
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Humboldt-Universität zu Berlin · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Institute of Pathology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 10117, Berlin, Germany
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Affiliation as printed
Department of Gynecology and Obstetrics, Goethe University, Frankfurt, Germany
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Affiliation as printed
Department of Gynecology and Obstetrics, Breast Cancer Center, Helios-Klinikum Berlin, Buch, Germany
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German Cancer Research Center · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), 69210, Heidelberg, Germany
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University Medical Center Hamburg-Eppendorf
Affiliation as printed
Department of Obstetrics and Gynecology, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany
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Humboldt-Universität zu Berlin · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Institute of Pathology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 10117, Berlin, Germany
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Affiliation as printed
Brustzentrum, Universitätsklinikum Erlangen, Erlangen, Germany
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Humboldt-Universität zu Berlin · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Institute of Pathology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 10117, Berlin, Germany
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University Hospital Heidelberg
Affiliation as printed
Department of Obstetrics and Gynecology, University Hospital Heidelberg, Heidelberg, Germany
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Affiliation as printed
Klinik für Gynäkologie und Geburtsmedizin, Universitätsklinikum Aachen, Aachen, Germany
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Humboldt-Universität zu Berlin · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Institute of Pathology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 10117, Berlin, Germany
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Philipps University of Marburg
Affiliation as printed
Institute of Pathology, Philipps-University Marburg and University Hospital Marburg, Marburg, Germany
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Affiliation as printed
Mammazentrum Hamburg, Hamburg, Germany
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German Cancer Research Center · Humboldt-Universität zu Berlin · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Deutsches Konsortium für Translationale Krebsforschung · Freie Universität Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Berlin Institute of Health, Anna-Louisa-Karsch-Straße 2, 10178, Berlin, Germany
German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), 69210, Heidelberg, Germany
Institute of Pathology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 10117, Berlin, Germany
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University Hospital Schleswig-Holstein
Affiliation as printed
University Hospital of Schleswig-Holstein, Campus Kiel, Germany
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Philipps University of Marburg
Affiliation as printed
Institute of Pathology, Philipps-University Marburg and University Hospital Marburg, Marburg, Germany
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Affiliation as printed
German Breast Group, 63263, Neu-Isenburg, Germany
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German Cancer Research Center · Humboldt-Universität zu Berlin · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Deutsches Konsortium für Translationale Krebsforschung · Freie Universität Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Berlin Institute of Health, Anna-Louisa-Karsch-Straße 2, 10178, Berlin, Germany
Department of Neuropathology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, 10117, Berlin, Germany
German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), 69210, Heidelberg, Germany
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