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Sci Rep. 2018 Apr 26;8(1):6574. doi: 10.1038/s41598-018-23733-4.

E-cadherin breast tumor expression, risk factors and survival: Pooled analysis of 5,933 cases from 12 studies in the Breast Cancer Association Consortium.

Author information

1
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
2
Division of Molecular Genetics & Pathology, US Food and Drug Administration, Silver Spring, MD, USA.
3
Department of Health Policy and Management, College of Health Science, Korea University, Seoul, Korea.
4
Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA.
5
Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
6
Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
7
Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands.
8
Cancer Epidemiology & Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
9
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global health, The University of Melbourne, Melbourne, Victoria, Australia.
10
Department of Pathology, Molecular Pathology and Therapeutic Targets Group, Hospital Universitario La Paz IdiPAZ, and Facultad de Medicina, Universidad Autonoma de Madrid, Madrid, Spain.
11
Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid, Spain.
12
Centro de Investigación en Red de Enfermedades Raras (CIBERER), Valencia, Spain.
13
Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
14
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
15
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
16
Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
17
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
18
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
19
Research Group Genetic Cancer Epidemiology, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
20
Independent contractor, CT(ASCP), MB (ASCP), National Cancer Institute, Bethesda, MD, USA.
21
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
22
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
23
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
24
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
25
Cancer Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
26
Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland.
27
Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland.
28
Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
29
Department of Pathology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
30
Saarland Cancer Registry, Saarbrücken, Germany.
31
Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
32
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
33
Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
34
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
35
The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.
36
Servicio de Cirugía General y Especialidades, Hospital Monte Naranco, Oviedo, Spain.
37
Department of Oncology, Mayo Clinic, Rochester, MN, USA.
38
Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.
39
Cancer Center, Kuopio University Hospital, Kuopio, Finland.
40
Institute of Clinical Medicine, Oncology, University of Eastern Finland, Kuopio, Finland.
41
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
42
Department of Pathology and Laboratory Medicin, Gillings School of Global Public Health, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
43
Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
44
Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands.
45
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. Jonine.figueroa@ed.ac.uk.
46
Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, UK. Jonine.figueroa@ed.ac.uk.

Abstract

E-cadherin (CDH1) is a putative tumor suppressor gene implicated in breast carcinogenesis. Yet, whether risk factors or survival differ by E-cadherin tumor expression is unclear. We evaluated E-cadherin tumor immunohistochemistry expression using tissue microarrays of 5,933 female invasive breast cancers from 12 studies from the Breast Cancer Consortium. H-scores were calculated and case-case odds ratios (OR) and 95% confidence intervals (CIs) were estimated using logistic regression. Survival analyses were performed using Cox regression models. All analyses were stratified by estrogen receptor (ER) status and histologic subtype. E-cadherin low cases (N = 1191, 20%) were more frequently of lobular histology, low grade, >2 cm, and HER2-negative. Loss of E-cadherin expression (score < 100) was associated with menopausal hormone use among ER-positive tumors (ever compared to never users, OR = 1.24, 95% CI = 0.97-1.59), which was stronger when we evaluated complete loss of E-cadherin (i.e. H-score = 0), OR = 1.57, 95% CI = 1.06-2.33. Breast cancer specific mortality was unrelated to E-cadherin expression in multivariable models. E-cadherin low expression is associated with lobular histology, tumor characteristics and menopausal hormone use, with no evidence of an association with breast cancer specific survival. These data support loss of E-cadherin expression as an important marker of tumor subtypes.

PMID:
29700408
PMCID:
PMC5920115
DOI:
10.1038/s41598-018-23733-4
[Indexed for MEDLINE]
Free PMC Article

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