Parallel Reaction Monitoring-Mass Spectrometry (PRM-MS)-Based Targeted Proteomic Surrogates for Intrinsic Subtypes in Breast Cancer: Comparative Analysis with Immunohistochemical Phenotypes

Advances in targeted medications have improved the survival rate of breast cancer patients with molecular marker-positive tumors. To date, immunohistochemistry (IHC) has remained as the standard method for quantifying the markers including HER2, ER, and PR. Nevertheless, IHC-based grading is subjective, because the results depend on trained individuals’ eye rather than numerical quantities. Thus, alternative methods that can account for quantitative levels of markers are gaining popularity, including targeted proteomics by mass spectrometry (MS). However, technical limitations have impeded the application of MS-based protein quantification to pathological FFPE slides that contain low amounts of cross-linked proteins. To challenge this, we developed a parallel reaction monitoring-mass spectrometry (PRM-MS) method to measure the expression levels of breast cancer markers. After developing the method using cell lines, we performed PRM-MS using 51 individuals’ FFPE samples. As a result, we obtained numerical ...