TY - JOUR
T1 - Loss of CDH1 (E-cadherin) expression is associated with infiltrative tumour growth and lymph node metastasis
AU - Kim, Sun A.
AU - Inamura, Kentaro
AU - Yamauchi, Mai
AU - Nishihara, Reiko
AU - Mima, Kosuke
AU - Sukawa, Yasutaka
AU - Li, Tingting
AU - Yasunari, Mika
AU - Morikawa, Teppei
AU - Fitzgerald, Kathryn C.
AU - Fuchs, Charles S.
AU - Wu, Kana
AU - Chan, Andrew T.
AU - Zhang, Xuehong
AU - Ogino, Shuji
AU - Qian, Zhi Rong
N1 - Funding Information:
This work was supported by U.S. National Institutes of Health (NIH) grants (K07 CA190673 to RN; R01 CA137178 and K24 DK098311 to ATC; P50 CA127003 to CSF; R01 CA151993 and R35 CA197735 to SO; P01 CA87969 and UM1 CA186107 to Meir J Stampfer, Nurse’s Health Study; P01 CA55075 and UM1 CA167552 to Walter C Willett, Health Professional’s Follow-up Study); grants from the Paula and Russell Agrusa Fund for Colorectal Cancer Research, the Friends of the Dana-Farber Cancer Institute, the Bennett Family Fund and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. SAK was supported by an early exchange postdoctoral fellowship grant from Asan Medical Center, Korea. KI was supported by a Japan Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad and by Takashi Tsuruo Memorial Fund, Japan. KM was supported by a fellowship grant from the Uehara Memorial Foundation, Japan. ATC is a Damon Runyon Clinical Investigator. We would like to thank the participants and staff of the Nurses’ Health Study and the Health Professionals Follow-up Study for their valuable contributions, as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. In addition, this study was approved by the Connecticut Department of Public Health (DPH) Human Investigations Committee. Use of standardised official symbols: We use HUGO (Human Genome Organisation)-approved official symbols for genes and gene products, including BRAF; CDH1 (so-called E-cadherin); CTNNB1 (catenin (cadherin-associated protein), beta 1, 88 kDa; so-called b-catenin); KRAS; and PIK3CA; all of which are described at www.genenames.org.
Funding Information:
This work was supported by U.S. National Institutes of Health (NIH) grants (K07 CA190673 to RN; R01 CA137178 and K24 DK098311 to ATC; P50 CA127003 to CSF; R01 CA151993 and R35 CA197735to SO; P01 CA87969 and UM1 CA186107 to Meir J Stampfer, Nurse''s Health Study; P01 CA55075 and UM1 CA167552 to Walter C Willett, Health Professional''s Follow-up Study); grants from the Paula and Russell Agrusa Fund for Colorectal Cancer Research, the Friends of the Dana-FarberCancer Institute, the Bennett Family Fund and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. SAK was supported by an early exchange postdoctoral fellowship grant from Asan Medical Center, Korea. KI was supported by a Japan Society for the Promotion of Science Postdoctoral Fellowshi for Research Abroad and by Takashi Tsuruo Memorial Fund, Japan. KM was supported by a fellowship grant from the Uehara Memorial Foundation, Japan. ATC is a Damon Runyon Clinical Investigator. We would like to thank the participants and staff of the Nurses'' Health Study and the Health Professionals Follow-up Study for their valuable contributions, as well as the following state cancer registries for theirhelp: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, N, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. In addition, this study was approvedby the Connecticut Department of Public Health (DPH) Human Investigations Committee. Use of standardised official symbols: We use HUGO (Human Genome Organisation)-approved official symbols for genes and gene products, including BRAF; CDH1 (so-called E-cadherin); CTNNB1 (catenin (cadherin-associated protein), beta 1, 88kDa; so-called b-catenin); KRAS; and PIK3CA; allof which are described at www.genenames.org. 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.
Publisher Copyright:
© 2016 Cancer Research UK.
PY - 2016/1/19
Y1 - 2016/1/19
N2 - 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.
AB - 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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U2 - 10.1038/bjc.2015.347
DO - 10.1038/bjc.2015.347
M3 - Article
C2 - 26742007
AN - SCOPUS:84955171910
SN - 0007-0920
VL - 114
SP - 199
EP - 206
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 2
ER -
