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Br J Cancer. 2016 Jan 19;114(2):199-206. doi: 10.1038/bjc.2015.347. Epub 2016 Jan 7.

Loss of CDH1 (E-cadherin) expression is associated with infiltrative tumour growth and lymph node metastasis.

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue M420, Boston, MA 02215, USA.
2
Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
3
Department of Nutrition, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue Building 2, room 213, Boston, MA 02115, USA.
4
Department of Geriatric Gastroenterology, Chinese PLA General Hospital, 28 Fuxing Road, Haidian, Beijing 100853, China.
5
Department of Pathology, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
6
Department of Epidemiology, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA.
7
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, 29 Wigglesworth Street, Boston, MA 02120, USA.
8
Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, GRJ-722, Boston, MA 02114, USA.
9
Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, 29 Wigglesworth Street, Boston, MA 02120, USA.

Abstract

BACKGROUND:

Loss of CDH1 (E-cadherin) expression in cancer cells may promote cell migration and invasion. Therefore, we hypothesised that loss of CDH1 expression in colorectal carcinoma might be associated with aggressive features and clinical outcome.

METHODS:

Utilising molecular pathological epidemiology database of 689 rectal and colon cancer cases in the Nurses' Health Study and the Health Professionals Follow-up Study, we assessed tumour CDH1 expression by immunohistochemistry. Multivariate logistic regression analysis was conducted to assess association of CDH1 loss with tumour growth pattern (expansile-intermediate vs infiltrative) and lymph node metastasis and distant metastasis, controlling for potential confounders including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and PIK3CA, BRAF and KRAS mutations. Mortality according to CDH1 status was assessed using Cox proportional hazards model.

RESULTS:

Loss of tumour CDH1 expression was observed in 356 cases (52%), and associated with infiltrative tumour growth pattern (odds ratio (OR), 2.02; 95% confidence interval (CI), 1.23-3.34; P=0.006) and higher pN stage (OR, 1.73; 95% CI, 1.23-2.43; P=0.001). Tumour CDH1 expression was not significantly associated with distant metastasis or prognosis.

CONCLUSIONS:

Loss of CDH1 expression in colorectal cancer is associated with infiltrative tumour growth pattern and lymph node metastasis.

PMID:
26742007
PMCID:
PMC4815802
DOI:
10.1038/bjc.2015.347
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

ATC previously served as a consultant for Bayer Healthcare, Millennium Pharmaceuticals, Pozen Inc and Pfizer Inc. This study was not funded by Bayer Healthcare, Millennium Pharmaceuticals, Pozen Inc, or Pfizer Inc. The remaining authors declare no conflicts of interest.

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