Tissue microarray-based studies of patients with lymph node negative breast carcinoma show that met expression is associated with worse outcome but is not correlated with epidermal growth factor family receptors
Tissue microarray-based studies of patients with lymph node negative breast carcinoma show that met expression is associated with worse outcome but is not correlated with epidermal growth factor family receptors
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DOI：
10.1002/cncr.11335
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发表时间：
2003-04-15
期刊：
影响因子：
6.2
通讯作者：
Rimm, DL
中科院分区：
文献类型：
--
作者：
Ocal, IT;Dolled-Filhart, M;Rimm, DL
背景已经显示受体酪氨酸激酶（RTK）预测乳腺癌患者预后。尽管RTK是一个大家族，但HER-2、表皮生长因子受体（EGFR）、Met（肝细胞生长因子受体）等都显示出预测结果的能力。然而，目前尚不清楚这些标志物是否定义了乳腺癌患者的同一亚群。在这项研究中，作者试图根据结果对人群进行分层的能力来确定RTK之间的相关性。方法。作者应用组织芯片技术研究了324例随访20-40年的淋巴结阴性乳腺癌患者。使用Met、EFGR、成纤维细胞生长因子受体（FGFR）和HER-2的免疫组织化学染色评估表达。表达水平通过。两个观察者，并分析相关性。同时收集标准病理学信息，包括肿瘤大小、核分级、Ki-67受体状态、雌激素和孕激素受体表达水平。研究队列中的RTK表达揭示了两种强相关性。HER-2与EGFR表达模式相似（P < 0.0001），Met胞浆区与FGFR胞浆染色表达模式相似（P < 0.0001），但两组间无相关性。在这些RTK中，只有高水平的Met胞质结构域作为预后标志物显示出与其他人群相比生存期缩短的意义（P = 0.0035;相对风险，2.04）。在同一组患者中，HER-2、激素受体状态和其他RTK家族受体与结局无关。在多因素分析中，只有Met胞浆结构域和肿瘤大小显示出独立的预测价值。目前的结果表明，Met的胞质结构域显示出独特的染色模式，并定义了一组独特的患者从HER-2，EGFR或激素受体的过表达定义的患者集。此外，这组患者与不良结局密切相关。(C)2003年美国癌症协会。
BACKGROUND. it has been shown that receptor tyrosine kinases (RTKs) predict outcome in patients with breast carcinoma. Although RTKs are a large family, HER-2, epidermal growth factor receptor (EGFR), Met (hepatocyte growth factor receptor), and others all have shown the ability to predict outcome. However, it remains unclear whether these markers are defining the same subpopulation of patients with breast carcinoma. In this study, the authors attempted to determine the correlation between RTKs on the basis of their ability to stratify a population according to outcome.METHODS. The authors used tissue microarray technology to study 324 patients with lymph node negative breast carcinoma who had 20-40 years of follow-up. Expression was assessed using immunohistochemical stains for Met, EFGR, fibroblast growth factor receptor (FGFR), and HER-2. Expression levels were assessed by. two observers, and correlations were analyzed. Standard pathology information, including tumor size, nuclear grade, Ki-67 receptor status, and estrogen and progesterone receptor expression levels, also was collected.RESULTS. RTK expression in the study cohort revealed two strong correlations. Specifically, HER-2 and EGFR showed similar expression patterns (P < 0.0001), and Met cytoplasmic domain and FGFR cytoplasmic staining showed similar expression patterns (P < 0.0001), but no correlation was found between the two groups. Of these RTKs, only high levels of Met cytoplasmic domain showed significance as a prognostic marker defining a shortened survival compared with the rest of the population (P = 0.0035; relative risk, 2.04). In the same group of patients, HER-2, hormone receptor status, and other RTK family receptors were not correlated with outcome. In multivariate analysis, only Met cytoplasmic domain and tumor size showed independent predictive value.CONCLUSIONS. The current results indicate that the cytoplasmic domain of Met shows a unique staining pattern and defines a set of patients unique from the set of patients defined by overexpression of HER-2, EGFR, or hormone receptors. Furthermore, this group of patients is associated tightly and independently with worse outcome. (C) 2003 American Cancer Society.