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

Joonho Park, Hyeon Jeong Oh, Dohyun Han, Joseph I. Wang, In Ae Park, Han Suk Ryu, Youngsoo Kim

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

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 measures of targets, quantifying 13 peptides of 4 markers in a single analysis per sample. The results correlated well with the IHC readings of experienced pathologists. Moreover, the results distinguished a gray zone in HER2 classification, which IHC alone failed to do. This proof-of-concept study demonstrates the application of targeted proteomics in pathologic slides, further supporting the applicability of MS-based approaches in precision medicine.

Original languageEnglish
Pages (from-to)2643-2653
Number of pages11
JournalJournal of Proteome Research
Volume19
Issue number7
DOIs
StatePublished - 2 Jul 2020

Keywords

  • breast cancer
  • formalin-fixed paraffin-embedded (FFPE) tissue
  • immunohistochemistry
  • molecular diagnostics
  • parallel reaction monitoring (PRM)
  • targeted proteomics

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