Poor prognosis in breast carcinomas correlates with increased expression of targetable CD146 and c-Met and with proteomic basal-like phenotype
Poor prognosis in breast carcinomas correlates with increased expression of targetable CD146 and c-Met and with proteomic basal-like phenotype
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DOI：
10.1016/j.humpath.2006.11.015
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发表时间：
2007-06-01
期刊：
影响因子：
3.3
通讯作者：
Charpin, Colette
中科院分区：
文献类型：
--
作者：
Garcia, Stephane;Dales, Jean-Philippe;Charpin, Colette
基因组研究导致了乳腺癌的新分类学分类。使用组织微阵列进行的蛋白质组学研究已经产生了互补的结果，并且有助于识别特定疗法的潜在分子靶点。寻找新的药物靶点对于预后不良的肿瘤尤为重要，例如缺乏雌激素受体和HER2扩增的乳腺肿瘤；在这些肿瘤中，某些分子可能在肿瘤通过基质微血管系统扩散的过程中发挥重要作用。我们根据患者生存情况（随访范围 4-10 年；中位随访 6.5 年）对 930 例乳腺癌进行了研究，使用（1）自动免疫组织化学程序（Ventana，Cedex，法国）和组织微阵列（Alphelys，Plaisir，法国）和（2）通过自动图像分析光密度测定法评估免疫沉淀物的定量（SAMBA，Meylan，法国）。比较了活着的和已故患者中 c-Met 和 CD146 的表达以及信号转导器 PI3K、FAK 和 FYN 的表达。还评估了最近报道的基底细胞癌特征的一些蛋白质的表达，即 CK5-6、caveolin-1、碳酸酐酶 IX、p63 和 CD117；这些也构成了侵袭性肿瘤治疗的潜在靶点。在死亡或转移患者中观察到这些蛋白质的过度表达（P
Genomic studies have led to new taxonomic classifications of breast carcinomas. Proteomic investigations using tissue microarrays have yielded complementary results and are useful in identifying potential molecular targets for specific therapies. Searching for new drug targets is particularly important for tumors of poor prognosis, such as breast tumors that lack estrogen receptors and HER2 amplification; in these tumors, certain molecules probably play a significant role in tumor spreading through the stromal microvasculature. We investigated 930 breast carcinomas categorized according to patients' survival (range of follow-up 4-10 years; median follow-up 6.5 years) using (1) automated immunohistochemical procedures (Ventana, Cedex, France) with tissue microarrays (Alphelys, Plaisir, France) and (2) quantification of immunoprecipitates assessed by automated image analysis densitometry (SAMBA, Meylan, France). Expression of c-Met and CD146 and that of signaling transducers PI3K, FAK, and FYN were compared in living and deceased patients. Expression of some proteins recently reported to be characteristic of basal cell carcinomas was also assessed, namely, CK5-6, caveolin-1, carbonic anhydrase IX, p63, and CD117; these also constitute potential targets for therapies for aggressive tumors. Overexpression of these proteins was observed in deceased or metastatic patients (P