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
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.
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 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.
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.
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.
Loss of CDH1 expression in colorectal cancer is associated with infiltrative tumour growth pattern and lymph node metastasis.
癌细胞中CDH1（E-钙黏蛋白）表达缺失可能促进细胞迁移和侵袭。因此，我们推测结直肠癌中CDH1表达缺失可能与侵袭性特征及临床结局相关。
利用护士健康研究和卫生专业人员随访研究中689例直肠癌和结肠癌病例的分子病理流行病学数据库，我们通过免疫组织化学评估肿瘤CDH1表达。进行多因素逻辑回归分析，以评估CDH1缺失与肿瘤生长模式（膨胀性-中间型与浸润型）、淋巴结转移及远处转移的关联，同时控制包括微卫星不稳定性、CpG岛甲基化表型、LINE-1甲基化以及PIK3CA、BRAF和KRAS突变等潜在混杂因素。使用Cox比例风险模型评估根据CDH1状态的死亡率。
356例（52%）病例中观察到肿瘤CDH1表达缺失，且与浸润性肿瘤生长模式相关（优势比（OR），2.02；95%置信区间（CI），1.23 - 3.34；P = 0.006）以及更高的pN分期相关（OR，1.73；95% CI，1.23 - 2.43；P = 0.001）。肿瘤CDH1表达与远处转移或预后无显著关联。
结直肠癌中CDH1表达缺失与浸润性肿瘤生长模式及淋巴结转移相关。
