Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA.
Am Soc Clin Oncol Educ Book. 2022 Apr;42:1-9. doi: 10.1200/EDBK_351207.
The increasing use of neoadjuvant therapy has resulted in therapeutic decisions being made on the basis of diagnostic needle core biopsy. For many patients, this method might yield the only fragment of tumor available for biomarker analysis, necessitating judicious use. Many multiplex protein analytic methods have been developed that employ fluorescence or other tags to overcome the limitations of immunohistochemistry while still retaining the spatial annotation. Interpretation of the data can be difficult because of the limitations of the human eye. Computational deconvolution of the signals may be necessary for some of these methods to enable identification of cell-specific localization and coexpression of biomarkers. Herein, we present the different methods that are coming of age and their application in cancer research, with a focus on breast cancer. We also discuss the limitations, which include high costs and long turnaround times. The methods are also based on the premise that preanalytical factors will have identical impact on all proteins analyzed. There is a need to establish standards to normalize the data and enable cross-sample comparisons. In spite of these limitations, the multiplex technologies are extremely valuable discovery tools and can provide novel insights into the biology of cancer and mechanisms of drug resistance.
新辅助治疗的应用越来越广泛，使得治疗决策基于诊断性的针芯活检。对于许多患者来说，这种方法可能仅提供用于生物标志物分析的肿瘤碎片，因此需要谨慎使用。已经开发出许多多重蛋白分析方法，这些方法使用荧光或其他标记物来克服免疫组织化学的局限性，同时仍然保留空间注释。由于人眼的局限性，对数据的解释可能很困难。对于其中一些方法，可能需要进行计算反卷积信号，以识别细胞特异性定位和生物标志物的共表达。本文介绍了日益成熟的不同方法及其在癌症研究中的应用，重点介绍了乳腺癌。我们还讨论了这些方法的局限性，包括高成本和较长的周转时间。这些方法还基于一个前提，即分析前因素对所有分析的蛋白质具有相同的影响。需要建立标准来规范数据并实现跨样本比较。尽管存在这些局限性，但多重技术仍然是非常有价值的发现工具，可以为癌症生物学和耐药机制提供新的见解。
