Jensen Kristian, Krusenstjerna-Hafstrøm Rikke, Lohse Jesper, Petersen Kenneth H, Derand Helene
Dako Denmark A/S, an Agilent Technologies Company, Produktionsvej 42, Glostrup, Denmark.
Mod Pathol. 2017 Feb;30(2):180-193. doi: 10.1038/modpathol.2016.176. Epub 2016 Oct 21.
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.
在当今临床常规病理学中,对完整的福尔马林固定石蜡包埋组织中的蛋白质检测仅限于半定量的免疫组织化学。本研究提出了一种新的可靠的定量免疫组织化学方法——qIHC,该方法基于一种新型扩增系统,通过计数点来直接对福尔马林固定石蜡包埋组织中的蛋白质进行定量。qIHC技术可与标准免疫组织化学相结合,并可使用标准明场显微镜或图像分析进行评估。目的是研究qIHC方法的分析性能。qIHC在分析定量检测的要求下进行测试,并与ELISA和流式细胞术进行定量蛋白质测量的比较。在五种不同的具有HER2表达的细胞系中测量人表皮生长因子受体2(HER2)蛋白表达,其HER2表达从免疫组织化学检测不到到强阳性染色(IHC 3+)。评估了重复性、再现性、稳健性、线性、动态范围、灵敏度和定量限。在使用商业免疫组织化学平台的类似实验室日常工作的设置中评估再现性和稳健性。此外,在44例乳腺癌标本中,qIHC与标准HER2免疫组织化学相关。对于所有评估参数,qIHC的性能与参考方法相当或更好。此外,qIHC的检测限低于免疫组织化学和ELISA参考方法,并证明能够在大动态范围内准确精确地测量HER2。总之,结果表明qIHC为福尔马林固定石蜡包埋细胞系和组织中的蛋白质表达测量提供了一种灵敏、定量、准确和稳健的检测方法。