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A novel quantitative immunohistochemistry method for precise protein measurements directly in formalin-fixed, paraffin-embedded specimens: analytical performance measuring HER2.

一项可在福尔马林固定、石蜡包埋样本中直接精确检测蛋白的新型定量方法:检测HER2的分析性能

Jensen K,Krusenstjerna-Hafstrøm R,Lohse J,Petersen KH,Derand H
阅读:821 Modern PathologyFeb 2017; 30 (2): 158 - 313:180-193 

Abstract

In clinical routine pathology today, detection of protein in intact formalin-fixed, paraffin-embedded tissue is limited to immunohistochemistry, which is semi-quantitative. This study presents a new and reliable quantitative immunohistochemistry method, qIHC, based on a novel amplification system that enables quantification of protein directly in formalin-fixed, paraffin-embedded tissue by counting of dots. The qIHC technology can be combined with standard immunohistochemistry, and assessed using standard bright-field microscopy or image analysis. The objective was to study analytical performance of the qIHC method. qIHC was tested under requirements for an analytical quantitative test, and compared with ELISA and flow cytometry for quantitative protein measurements. Human epidermal growth factor receptor 2 (HER2) protein expression was measured in five different cell lines with HER2 expression from undetectable with immunohistochemistry to strong positive staining (IHC 3+). Repeatability, reproducibility, robustness, linearity, dynamic range, sensitivity, and quantification limits were evaluated. Reproducibility and robustness were assessed in a setup to resemble daily work in a laboratory using a commercial immunohistochemistry platform. In addition, qIHC was correlated to standard HER2 immunohistochemistry in 44 breast cancer specimens. For all evaluated parameters, qIHC performance was either comparable or better than the reference methods. Furthermore, qIHC has a lower limit of detection than both immunohistochemistry and the ELISA reference method, and demonstrated ability to measure HER2 accurately and precise within a large dynamic range. In conclusion, the results show that qIHC provides a sensitive, quantitative, accurate, and robust assay for measurement of protein expression in formalin-fixed, paraffin-embedded cell lines, and tissue.

摘要

临床常规病理检测的今天,应用免疫组织化学方法在完整的福尔马林固定、石蜡包埋组织中检测蛋白是有局限性的,因为免疫组织化学方法是半定量的。本研究推出一项新的、可靠的定量免疫组织化学方法:qIHC,此方法是建立在新的扩增系统上,能在福尔马林固定、石蜡包埋的组织中通过计数点的多少使蛋白质量化。qIHC技术与标准的免疫组织化学结合,用标准的亮视野显微镜术和图像分析进行评估。本目的是研究qIHC方法的分析性能。qIHC需要在分析性的定量检测下,结合ELISA和流式细胞术进行定量蛋白的检测。在5种不同的细胞系中检测人类表皮生长因子受体2(HER2)蛋白的表达,HER2在这些细胞系中免疫组织化学强阳性(IHC 3+)。我们对此方法的重复性、再现性、稳定性、线性关系、动态范围、敏感性和定量局限进行评估。再现性和稳定性应用商业性免疫组织化学平台,在实验室已建立的类似的日常工作中进行评估。此外,qIHC与44个乳腺癌样本中标准的HER2免疫组织化学有关。在所有评估的参数中,qIHC性能比得上或优于参考方法。而且, qIHC比免疫组织化学和ELISA 的参考方法有更低的检测局限性,并证实能在较大动态范围内精确检测HER2。总之,结果显示 qIHC方法能在福尔马林固定、石蜡包埋的细胞系和组织中对蛋白表达的检测提供灵敏定量的、精确的和稳定的分析。

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