Expression of extracellular matrix metalloproteases inducer on micrometastatic and primary mammary carcinoma cells
Expression of extracellular matrix metalloproteases inducer on micrometastatic and primary mammary carcinoma cells
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DOI：
10.1158/1078-0432.ccr-03-0610
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发表时间：
2004-05-15
影响因子：
11.5
通讯作者：
Pantel, K
中科院分区：
文献类型：
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作者：
Reimers, N;Zafrakas, K;Pantel, K
目的：EMMPRIN（细胞外基质金属蛋白酶诱导剂）是免疫球蛋白超家族的一个糖基化成员，已知可刺激肿瘤周围成纤维细胞中基质金属蛋白酶（MMPs） 1、2、3和MT1-MMP的产生。我们在这里评估了EMMPRIN的表达是否与人类乳腺癌的肿瘤进展有关。实验设计：采用高密度组织微阵列（n = 2222例乳腺癌样本）和emmprinn特异性抗体HIM6和memm - m6 /1进行免疫组化研究，染色结果与各种临床病理参数具有统计学相关性。为了分析EMMPRIN表达与骨髓微转移之间的可能关联，我们将另外55例乳腺肿瘤纳入了我们的研究，这些肿瘤是用抗细胞角蛋白抗体A45-B/B3检测的，它们来自有或没有微转移细胞的患者。用emmprin1特异性抗体1G6.2检测BM细胞角蛋白阳性细胞。结果：EMMPRIN阳性与多种组织病理危险因素（肿瘤分级高、肿瘤大小增大、雌激素受体和孕激素受体状态阴性、有丝分裂指数升高）及肿瘤特异性生存率降低相关（log-rank, P = 0.0027）。Cox回归分析显示，特别是在50岁至50岁的患者（即绝经后妇女）中，EMMPRIN表达是一个独立的预后因素（相对风险= 1.7,95%置信区间为1.4-4.3,P = 0.036）。EMMPRIN在BM中接近90%的微转移细胞中表达，这一事实也支持了EMMPRIN在肿瘤进展中的参与。结论：EMMPRIN在原发肿瘤中的表达预示着乳腺癌的不良预后，提示EMMPRIN在人类乳腺癌的进展中起着重要作用。
Purpose: EMMPRIN (extracellular matrix metalloprotease inducer) is a glycosylated member of the immunoglobulin superfamily known to stimulate the production of matrix metalloproteases (MMPs) 1, 2, and 3 and MT1-MMP in peritumoral fibroblasts. We here evaluated whether EMMPRIN expression is related to tumor progression in human breast cancer.Experimental Design: An immumohistochemical study using high-density tissue microarrays (n = 2222 breast cancer samples) and EMMPRIN-specific antibodies HIM6 and MEM-M6/1 was performed, and staining results were statistically correlated with various clinicopathological parameters. To analyze the putative association between EMMPRIN expression and bone marrow (BM) micrometastasis, an additional set of 55 breast tumors from patients with or without micrometastatic cells as determined with anti-cytokeratin antibody A45-B/B3 were included in our study. Cytokeratin-positive cells in BM were costained with EMMPRIN-specific antibody 1G6.2.Results: Positive EMMPRIN staining correlated significantly with various histopathological risk factors (higher tumor grade, increased tumor size, negative estrogen receptor status and progesterone receptor status, and higher mitotic index) as well as decreased tumor-specific survival (log-rank, P = 0.0027). In particular, in patients > 50 years (i.e., postmenopausal women), EMMPRIN expression was an independent prognosticator as shown by Cox regression analysis (relative risk = 1.7, 95% confidence interval 1.4-4.3, P = 0.036). An involvement of EMMPRIN in tumor progression was also supported by the fact that it was expressed on similar to90% of micrometastatic cells in BM.Conclusions: EMMPRIN expression in primary tumor predicts an unfavorable prognosis in breast cancer, suggesting a crucial role of EMMPRIN in progression of human mammary carcinomas.