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

• Published in: British journal of cancer 2016-01, Vol.114 (2), p.199-206
• Main Authors: Kim, Sun A, Inamura, Kentaro, Yamauchi, Mai, Nishihara, Reiko, Mima, Kosuke, Sukawa, Yasutaka, Li, Tingting, Yasunari, Mika, Morikawa, Teppei, Fitzgerald, Kathryn C, Fuchs, Charles S, Wu, Kana, Chan, Andrew T, Zhang, Xuehong, Ogino, Shuji, Qian, Zhi Rong
• Format: Article
• Language: English
• Subjects: 631/337/458/1648; 692/4028/67/1504/1885; 692/4028/67/322; 692/420/755; Adaptor Proteins, Signal Transducing - genetics; Aged; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Cadherins - metabolism; Cancer Research; Carcinoma - metabolism; Carcinoma - mortality; Carcinoma - pathology; Cell adhesion & migration; Cell Movement; Class I Phosphatidylinositol 3-Kinases; Cohort Studies; Colorectal cancer; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; CpG Islands; Databases, Factual; Disease Progression; DNA Methylation; Drug Resistance; Epidemiology; Female; Gastroenterology; Hospitals; Humans; Immunohistochemistry; Logistic Models; Long Interspersed Nucleotide Elements; Lymph Nodes - pathology; Lymphatic Metastasis; Lymphatic system; Male; Medical personnel; Medical prognosis; Medical schools; Metastasis; Microsatellite Instability; Middle Aged; Molecular Medicine; Mortality; Multivariate Analysis; Mutation; MutL Protein Homolog 1; Neoplasm Invasiveness; Neoplasm Staging; Nuclear Proteins - genetics; Odds Ratio; Oncology; Pathology; Phosphatidylinositol 3-Kinases - genetics; Prognosis; Promoter Regions, Genetic; Proportional Hazards Models; Prospective Studies; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins p21(ras) - genetics; Public health; Translational Therapeutics
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2015.347

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.