Vimentin as a poor prognostic factor for triple-negative breast cancer
Vimentin as a poor prognostic factor for triple-negative breast cancer
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DOI：
10.1007/s00432-013-1376-6
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发表时间：
2013-05-01
影响因子：
3.6
通讯作者：
Maehara, Yoshihiko
中科院分区：
文献类型：
--
作者：
Yamashita, Nami;Tokunaga, Eriko;Maehara, Yoshihiko
三阴性乳腺癌(TNBC)是一种高度异质性疾病，以雌激素受体、孕激素受体和人表皮生长因子受体2缺失为特征。最近的研究表明，TNBC与上皮-间充质转化(EMT)之间存在联系。为了确定预后的生物标志物和新的治疗靶点，波形蛋白是TNBC中与EMT相关的最主要因素之一，我们从659例日本人的浸润性导管癌标本中获得了90例(14%)的TNBC。用定量逆转录聚合酶链式反应和免疫组织化学方法检测Vimentin的mRNA和蛋白表达水平，发现Vimentin在基底层乳腺癌细胞系中的表达明显上调。免疫组织化学显示，波形蛋白在TNBC中的表达显著高于其他亚型(p=0.0042)。波形蛋白表达与TNBC患者年龄较小(p=0.016)、核级别高(p=0.023)和Ki67高表达(p<；0.0001)有关，其无复发生存期(RFs)(p=0.0058)和总生存期(OS)(p=0.013)的预后较差。多因素分析显示，波形蛋白表达是影响远期生存率的独立预后因素(p=0.043)。在基底细胞样乳腺癌患者中，波形蛋白的表达还与患者的RFS(p=0.021)和OS(p=0.017)显著相关，波形蛋白的高表达与肿瘤的侵袭性表型和不良预后有关。波形蛋白的表达可作为判断TNBC预后的生物标志物。
Triple-negative breast cancer (TNBC), characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, is a highly heterogeneous disease. Recent studies suggest that there are links between TNBC and the epithelial-mesenchymal transition (EMT). To identify prognostic biomarkers and novel therapeutic targets, vimentin, one of the most major factors associated with EMT was investigated in TNBC.Sporadic invasive ductal carcinoma specimens were obtained from 659 Japanese patients, and 90 (14 %) cases were diagnosed as TNBC. The vimentin mRNA and protein expression levels were evaluated by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry.The mRNA expression of vimentin was significantly upregulated in the basal-type breast cancer cell line. Immunohistochemically, the vimentin expression was significantly higher (p = 0.0042) in TNBC compared with the other subtypes. Vimentin expression was associated with a younger age (p = 0.016), high nuclear grade (p = 0.023) and high Ki67 expression (p < 0.0001), and a poorer prognosis in terms of both the recurrence-free survival (RFS) (p = 0.0058) and overall survival (OS) (p = 0.013) in TNBC patients. A multivariate analysis showed that vimentin expression was an independent prognostic factor for the RFS (p = 0.043). Vimentin expression was also associated with a significantly shorter RFS (p = 0.021) and OS (p = 0.017) in patients with basal-like breast cancer (BLBC).The elevated expression of vimentin contributes to the aggressive phenotype and poor prognosis in TNBC. Vimentin expression might be useful as a biomarker for the prognosis of TNBC.