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. 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

Sun A Kim  1 , Kentaro Inamura  1   2 , Mai Yamauchi  1 , Reiko Nishihara  1   3 , Kosuke Mima  1 , Yasutaka Sukawa  1 , Tingting Li  1   4 , Mika Yasunari  1 , Teppei Morikawa  5 , Kathryn C Fitzgerald  6 , Charles S Fuchs  1   7 , Kana Wu  3 , Andrew T Chan  7   8 , Xuehong Zhang  7 , Shuji Ogino  1   6   9 , Zhi Rong Qian  1
Affiliations

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

Sun A Kim et al. Br J Cancer. .

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.

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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.

Figures

Figure 1
Figure 1
Tumour growth pattern. (A) Expansile growth pattern is defined by pushing and well-circumscribed tumour border. (B) Intermediate growth pattern is defined by tumour border blurred by invasion of large or medium-sized tumour glands. (C) Infiltrative growth pattern is designated when small tumour glands or irregular clusters or cords of tumour cells infiltrate in a diffuse manner without distinct border. Haematoxylin and eosin stain, original magnification × 40.
Figure 2
Figure 2
CDH1 immunohistochemistry. (A) Lack of staining in tumour cell membrane is interpreted as loss of CDH1 expression. (B) Brown staining in complete circumference of tumour cell membrane is interpreted as intact CDH1 expression. Original magnification × 400.
See this image and copyright information in PMC

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