Loss of CDH1 (E-cadherin) expression is associated with infiltrative tumour growth and lymph node metastasis.
Loss of CDH1 (E-cadherin) expression is associated with infiltrative tumour growth and lymph node metastasis.
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DOI：
10.1038/bjc.2015.347
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发表时间：
2016-01-19
影响因子：
8.8
通讯作者：
Qian ZR
中科院分区：
文献类型：
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作者：
Kim SA;Inamura K;Yamauchi M;Nishihara R;Mima K;Sukawa Y;Li T;Yasunari M;Morikawa T;Fitzgerald KC;Fuchs CS;Wu K;Chan AT;Zhang X;Ogino S;Qian ZR
CDH 1（E-cadherin）在癌细胞中表达的缺失可促进细胞迁移和侵袭。因此，我们推测，CDH 1表达的损失可能与大肠癌的侵袭性特征和临床结果。利用分子病理流行病学数据库中的689例直肠癌和结肠癌病例的护士健康研究和卫生专业人员随访研究，我们评估了肿瘤CDH 1的表达免疫组化。进行多变量逻辑回归分析，以评估CDH 1丢失与肿瘤生长模式（扩张性-中间型vs浸润性）以及淋巴结转移和远处转移的相关性，控制潜在混杂因素，包括微卫星不稳定性、CpG岛甲基化表型、LINE-1甲基化以及PIK 3CA、BRAF和KRAS突变。使用考克斯比例风险模型评估根据CDH 1状态的死亡率。在356例（52%）病例中观察到肿瘤CDH 1表达缺失，并与浸润性肿瘤生长模式（比值比（OR），2.02; 95%置信区间（CI），1.23-3.34; P=0.006）和较高pN分期（OR，1.73; 95% CI，1.23-2.43; P=0.001）相关。肿瘤CDH 1表达与远处转移或预后无显著相关。结肠直肠癌中CDH 1表达的缺失与浸润性肿瘤生长模式和淋巴结转移相关。
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.