Nestin expression in breast cancer: association with prognosis and subtype on 3641 cases with long-term follow-up.

Nestin expression in breast cancer: association with prognosis and subtype on 3641 cases with long-term follow-up.
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DOI:
10.1007/s10549-017-4583-z
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发表时间:
2018-03
影响因子:
3.8
通讯作者:
Nielsen TO
Nielsen TO
中科院分区:
医学2区
文献类型:
--
作者:
Asleh K;Won JR;Gao D;Voduc KD;Nielsen TO

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基底样乳腺癌最初通过基因表达谱识别,可使用需要雌激素受体(ER)阴性的免疫组织化学(IHC)定义进行临床鉴定。然而,一些基础病例是ER阳性的,并且被标准IHC方法错误地认为是管腔性的,导致次优的治疗选择。Nestin是一种在许多干细胞中表达的中间丝,是一种新近发现的基底样表型的阳性标记物,与ER状态无关。在这项研究中,我们在一个大型乳腺癌队列中评估了其临床相关性和预后能力。通过免疫组化法对一系列临床注释的浸润性乳腺癌组织微阵列进行巢蛋白表达评估,中位随访时间为12.6年。Kaplan-Meier和考克斯回归模型用于评估巢蛋白状态对主要终点乳腺癌特异性生存期(BCSS)的预后意义。在3641例可通过IHC解释巢蛋白的病例中,在371例(10%)中发现了阳性染色,并且与不良预后因素(包括基底样分化的其他标志物)显著相关。nestin阳性肿瘤患者的10年BCSS显著较低(HR=1.97,95%CI:1.62-2.40; P<0.001)。重要的是,在2323例ER+病例的大组中,巢蛋白阳性确定了120例患者(5%)的亚组,其10年BCSS显著较差(HR=1.50,95%CI:1.10-2.13; P=0.02)。巢蛋白免疫组化阳性与不良的临床结果和降低的生存率相关,这是基因表达基底样亚型的特征。这种易于应用的工具可识别目前被“三阴性”或“核心基础”IHC定义遗漏的ER+预后不良基础表型患者。
Basal-like breast cancers, originally recognized by gene expression profiling, can be clinically identified using immunohistochemical (IHC) definitions that require estrogen receptor (ER) negativity. However, some basal cases are ER-positive and are mistakenly considered to be luminal by standard IHC approaches, leading to suboptimal treatment choices. Nestin, an intermediate filament expressed in many stem cells, is a recently-identified positive marker of basal-like phenotype independent of ER status. In this study we evaluated its clinical associations and prognostic capacity in a large breast cancer cohort. A tissue microarray series of clinically-annotated invasive breast cancers with 12.6 years median follow-up was assessed for nestin expression by IHC. Kaplan-Meier and Cox regression models were used to evaluate the prognostic significance of nestin status, for the primary endpoint of breast-cancer-specific-survival (BCSS). Among 3641 cases interpretable for nestin by IHC, positive staining was found in 371 cases (10%) and was significantly associated with poor prognostic factors including other markers of basal-like differentiation. Patients with nestin-positive tumors had a significantly lower 10 year BCSS (HR=1.97, 95%CI: 1.62–2.40; P<0.001). Importantly, within the large group of 2323 ER+ cases, nestin positivity identified a subgroup of 120 patients (5%) with a significantly inferior 10 years BCSS (HR=1.50, 95%CI: 1.10–2.13; P=0.02). Nestin IHC positivity is associated with the poor clinical outcomes and reduced survival rates that characterize the gene expression basal-like subtype. This easily-applicable tool identifies ER+ poor prognosis basal phenotype patients that are currently being missed by “Triple-negative” or “Core basal” IHC definitions.
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