Format

Send to

Choose Destination
Lab Invest. 2018 Jan;98(1):117-129. doi: 10.1038/labinvest.2017.106. Epub 2017 Oct 16.

Lobular carcinoma in situ and invasive lobular breast cancer are characterized by enhanced expression of transcription factor AP-2β.

Author information

1
Institute of Pathology, Hannover Medical School, Hannover, Germany.
2
Institute of Laboratory Animal Science, Hannover Medical School, Hannover, Germany.
3
Department of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland.
4
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
5
Division of Molecular Pathology, the Netherlands Cancer Institute, Amsterdam, The Netherlands.
6
Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany.
7
West German Study Group, Moenchengladbach, Germany.
8
Breast Center Niederrhein, Evangelic Bethesda Hospital, Moenchengladbach, Germany.
9
Breast Center, Department of Obstetrics and Gynecology, University of Munich, Munich, Germany.

Abstract

Transcription factor AP-2β (TFAP2B) regulates embryonic organ development and is overexpressed in alveolar rhabdomyosarcoma, a rare childhood malignancy. Gene expression profiling has implicated AP-2β in breast cancer (BC). This study characterizes AP-2β expression in the mammary gland and in BC. AP-2β protein expression was assessed in the normal mammary gland epithelium, in various reactive, metaplastic and pre-invasive neoplastic lesions and in two clinical BC cohorts comprising >2000 patients. BCs from various genetically engineered mouse (GEM) models were also evaluated. Human BC cell lines served as functional models to study siRNA-mediated inhibition of AP-2β. The normal mammary gland epithelium showed scattered AP-2β-positive cells in the luminal cell layer. Various reactive and pre-invasive neoplastic lesions, including apocrine metaplasia, usual ductal hyperplasia and lobular carcinoma in situ (LCIS) showed enhanced AP-2β expression. Cases of ductal carcinoma in situ (DCIS) were more often AP-2β-negative (P<0.001). In invasive BC cohorts, AP-2β-positivity was associated with the lobular BC subtype (P<0.001), loss of E-cadherin (P<0.001), a positive estrogen receptor (ER) status (P<0.001), low Ki67 (P<0.001), low/intermediate Oncotype DX recurrence scores (P<0.001), and prolonged event-free survival (P=0.003). BCs from GEM models were all AP-2β-negative. In human BC cell lines, AP-2β expression was independent from ER-signaling. SiRNA-mediated inhibition of AP-2β diminished proliferation of lobular BC cell lines in vitro. In summary, AP-2β is a new mammary epithelial differentiation marker. Its expression is preferentially retained and enhanced in LCIS and invasive lobular BC and has prognostic implications. Our findings indicate that AP-2β controls tumor cell proliferation in this slow-growing BC subtype.

PMID:
29035379
DOI:
10.1038/labinvest.2017.106
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center