Department of Pathology and Laboratory Medicine, Genetic Pathology Evaluation Centre, University of British Columbia, 509-2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
Department of Pathology and Laboratory Medicine, Canadian Immunohistochemistry Quality Control (CIQC), University of British Columbia, G408-2211 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada.
Breast Cancer Res Treat. 2018 Feb;168(1):107-115. doi: 10.1007/s10549-017-4583-z. Epub 2017 Nov 20.
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-year 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-year 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.
基底样乳腺癌最初通过基因表达谱识别，可以通过需要雌激素受体 (ER) 阴性的免疫组织化学 (IHC) 定义在临床上识别。然而，一些基底病例 ER 阳性，并且由于标准 IHC 方法错误地被认为是管腔，导致治疗选择不理想。巢蛋白是一种在许多干细胞中表达的中间丝，是一种最近被鉴定的与 ER 状态无关的基底样表型的阳性标志物。在这项研究中，我们在一个大型乳腺癌队列中评估了它的临床相关性和预后能力。
对具有 12.6 年中位随访的临床注释的浸润性乳腺癌的组织微阵列系列进行巢蛋白免疫组织化学评估。使用 Kaplan-Meier 和 Cox 回归模型评估巢蛋白状态对乳腺癌特异性生存 (BCSS) 的主要终点的预后意义。
在 3641 例可通过 IHC 解释巢蛋白的病例中，发现 371 例（10%）染色阳性，与包括其他基底样分化标志物在内的不良预后因素显著相关。巢蛋白阳性肿瘤患者的 10 年 BCSS 显著降低（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，巢蛋白阳性确定了一个亚组，其中 120 例患者（5%）的 10 年 BCSS 显著降低（HR 1.50，95%CI 1.10-2.13；P=0.02）。
巢蛋白 IHC 阳性与基因表达基底样亚型的不良临床结局和生存率降低相关。这种易于应用的工具可以识别 ER+预后不良的基底表型患者，这些患者目前被“三阴性”或“核心基底”IHC 定义所遗漏。
