title: Loss of CDH1 (E-cadherin) expression is associated with infiltrative tumour growth and lymph node metastasis.
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.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue M420, Boston, MA 02215, USA.
authors.forename: Sun A
authors.initials: SA
authors.lastname: Kim
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue M420, Boston, MA 02215, USA.|Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Inamura
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue M420, Boston, MA 02215, USA.
authors.forename: Mai
authors.initials: M
authors.lastname: Yamauchi
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue M420, Boston, MA 02215, USA.|Department of Nutrition, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue Building 2, room 213, Boston, MA 02115, USA.
authors.forename: Reiko
authors.initials: R
authors.lastname: Nishihara
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue M420, Boston, MA 02215, USA.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Mima
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue M420, Boston, MA 02215, USA.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Sukawa
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue M420, Boston, MA 02215, USA.|Department of Geriatric Gastroenterology, Chinese PLA General Hospital, 28 Fuxing Road, Haidian, Beijing 100853, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue M420, Boston, MA 02215, USA.
authors.forename: Mika
authors.initials: M
authors.lastname: Yasunari
authors.affiliation: Department of Pathology, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Morikawa
authors.affiliation: Department of Epidemiology, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Kathryn C
authors.initials: KC
authors.lastname: Fitzgerald
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue M420, Boston, MA 02215, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, 29 Wigglesworth Street, Boston, MA 02120, USA.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue Building 2, room 213, Boston, MA 02115, USA.
authors.forename: Kana
authors.initials: K
authors.lastname: Wu
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, 29 Wigglesworth Street, Boston, MA 02120, USA.|Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, GRJ-722, Boston, MA 02114, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, 29 Wigglesworth Street, Boston, MA 02120, USA.
authors.forename: Xuehong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue M420, Boston, MA 02215, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA.|Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, 29 Wigglesworth Street, Boston, MA 02120, USA.
authors.forename: Shuji
authors.initials: S
authors.lastname: Ogino
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue M420, Boston, MA 02215, USA.
authors.forename: Zhi Rong
authors.initials: ZR
authors.lastname: Qian
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000368:Aged; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002465:Cell Movement; D058534:Class I Phosphatidylinositol 3-Kinases; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D016208:Databases, Factual; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D020084:Long Interspersed Nucleotide Elements; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D015999:Multivariate Analysis; D000070957:MutL Protein Homolog 1; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics; D016017:Odds Ratio; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; C117307:KRAS protein, human; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000070957:MutL Protein Homolog 1; D016283:Proto-Oncogene Proteins p21(ras)