Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma
Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma
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DOI：
10.1158/1078-0432.ccr-04-0220
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发表时间：
2004-08-15
影响因子：
11.5
通讯作者：
Perou, CM
中科院分区：
文献类型：
--
作者：
Nielsen, TO;Hsu, FD;Perou, CM
目的：表达谱研究将乳腺癌分为雌激素受体（ER）+/管腔型、正常乳腺样、HER 2过表达和基底样组，后两者与不良结局相关。目前，存在临床检测，确定ER+/管腔和HER 2过表达的肿瘤，我们试图开发一种临床检测乳腺基底样tumors.Experimental设计：为了确定乳腺基底样肿瘤的免疫组化概况，我们收集了一系列已知的基底样肿瘤，并测试它们的蛋白质模式，这是该亚型的特征。接下来，我们研究了这些蛋白质模式的意义，使用组织微阵列和评估这些findings.Results的预后意义：使用一组21基底样肿瘤，这是确定使用基因表达谱，我们看到，这种亚型是典型的雌激素受体和HER 2，但阳性的基础细胞角蛋白，HER 1，和/或c-KIT的免疫化学阴性。使用代表930例平均随访17.4年的乳腺癌组织微阵列，基础细胞角蛋白表达与低疾病特异性生存率相关。在54%的基底细胞角蛋白阳性病例中观察到HER 1表达（阴性病例为11%），与生存率低相关，与淋巴结状态和大小无关。c-KIT的表达是更常见的基底样肿瘤比其他乳腺cancer.Conclusions，但不影响预后：一个面板的四种抗体（ER，HER 1，HER 2，和细胞角蛋白5/6）可以准确地识别基底样肿瘤使用标准的临床工具，并显示出高特异性。这些研究表明，许多基底细胞样肿瘤表达HER 1，这表明候选药物在这些患者中进行评估。
Purpose: Expression profiling studies classified breast carcinomas into estrogen receptor (ER)+/luminal, normal breast-like, HER2 overexpressing, and basal-like groups, with the latter two associated with poor outcomes. Currently, there exist clinical assays that identify ER+/luminal and HER2-overexpressing tumors, and we sought to develop a clinical assay for breast basal-like tumors.Experimental Design: To identify an immunohistochemical profile for breast basal-like tumors, we collected a series of known basal-like tumors and tested them for protein patterns that are characteristic of this subtype. Next, we examined the significance of these protein patterns using tissue microarrays and evaluated the prognostic significance of these findings.Results: Using a panel of 21 basal-like tumors, which was determined using gene expression profiles, we saw that this subtype was typically immunohistochemically negative for estrogen receptor and HER2 but positive for basal cytokeratins, HER1, and/or c-KIT. Using breast carcinoma tissue microarrays representing 930 patients with 17.4-year mean follow-up, basal cytokeratin expression was associated with low disease-specific survival. HER1 expression was observed in 54% of cases positive for basal cytokeratins (versus 11% of negative cases) and was associated with poor survival independent of nodal status and size. c-KIT expression was more common in basal-like tumors than in other breast cancers but did not influence prognosis.Conclusions: A panel of four antibodies (ER, HER1, HER2, and cytokeratin 5/6) can accurately identify basal-like tumors using standard available clinical tools and shows high specificity. These studies show that many basal-like tumors express HER1, which suggests candidate drugs for evaluation in these patients.