Park Daehoon, Kåresen Rolf, Axcrona Ulrika, Noren Tove, Sauer Torill
Department of Pathology, Ullevaal University Hospital, Oslo, Norway.
APMIS. 2007 Jan;115(1):52-65. doi: 10.1111/j.1600-0463.2007.apm_524.x.
Reduced intercellular adhesion is implicated in the development of metastasis. This study investigates the expression of intercellular adhesion molecules (E-cadherin, alpha-, beta-, gamma-catenin and claudin-7) and their influence on survival in primary breast carcinomas and corresponding axillary lymph node metastases (ALNM), and evaluates associations between them and with clinicopathological factors. The expression of adhesion molecules was analyzed immunohistochemically in tissues from 196 patients with primary invasive breast carcinomas and their nodal metastases (174 ductal and 22 lobular types). The expression was evaluated using semi-quantitative scoring of the intensity and proportion of immunoreactivity. All five adhesion proteins showed significantly reduced expression in primary ductal carcinomas with re-expression in ALNM (p<0.001). In uni- and multivariate analyses, the expression of E-cadherin in the primary tumours was a significant predictor of disease-free survival and distant disease-free survival. Thus, abnormal E-cadherin expression in the primary invasive breast carcinoma seems to be an independent prognostic biomarker in predicting a shorter survival in node-positive breast cancer patients. The results indicate that abnormal expression of the adhesion molecules in the primary tumours with re-expression in corresponding nodal metastases is a common event in breast ductal carcinomas and may play a central role in establishing metastasis.
细胞间黏附力降低与转移的发生有关。本研究调查了细胞间黏附分子(E-钙黏蛋白、α-、β-、γ-连环蛋白和闭合蛋白-7)的表达及其对原发性乳腺癌和相应腋窝淋巴结转移灶(ALNM)生存的影响,并评估它们之间以及与临床病理因素的关联。采用免疫组织化学方法分析了196例原发性浸润性乳腺癌患者及其淋巴结转移灶(174例导管型和22例小叶型)组织中黏附分子的表达。使用免疫反应强度和比例的半定量评分来评估表达情况。所有五种黏附蛋白在原发性导管癌中的表达均显著降低,而在ALNM中重新表达(p<0.001)。在单因素和多因素分析中,原发性肿瘤中E-钙黏蛋白的表达是无病生存期和远处无病生存期的重要预测指标。因此,原发性浸润性乳腺癌中E-钙黏蛋白的异常表达似乎是预测淋巴结阳性乳腺癌患者生存期较短的独立预后生物标志物。结果表明,原发性肿瘤中黏附分子的异常表达并在相应淋巴结转移灶中重新表达在乳腺导管癌中是常见现象,可能在转移的形成中起核心作用。