학술논문
DNA methylation profiling identifies two distinct subgroups in breast cancers with low hormone receptor expression, mainly associated with HER2 amplification status
Document Type
Original Paper
Author
Jurmeister, Philipp; Weber, Karsten; Villegas, Sonia; Karn, Thomas; Untch, Michael; Thieme, Anne; Müller, Volkmar; Taube, Eliane; Fasching, Peter; Schmitt, Wolfgang D.; Marmé, Frederik; Stickeler, Elmar; Sinn, Bruno V.; Jank, Paul; Schem, Christian; Klauschen, Frederick; van Mackelenbergh, Marion; Denkert, Carsten; Loibl, Sibylle; Capper, David
Source
Clinical Epigenetics. 13(1)
Subject
Language
English
ISSN
1868-7075
1868-7083
1868-7083
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.