Classification of Colorectal Cancer in Molecular Subtypes by Immunohistochemistry

Methods Mol Biol. 2018:1765:179-191. doi: 10.1007/978-1-4939-7765-9_11.


Colorectal cancer (CRC) is a heterogeneous disease, which can be categorized into distinct consensus molecular subtypes (CMSs). These subtypes differ in both clinical as well as biological properties. The gold-standard classification strategy relies on genome-wide expression data, which hampers widespread implementation. Here we describe an immunohistochemical (IHC) Mini Classifier, a practical tool that, in combination with microsatellite instability testing, delivers objective and accurate scoring to classify CRC patients into the main molecular disease subtypes. It is a robust immunohistochemical-based assay containing four specific stainings (FRMD6, ZEB1, HTR2B, and CDX2) in combination with cytokeratin. We also describe an online tool for classification of individual samples based on scoring parameters of these stainings.

Keywords: CMS; CRC; Classification; Colorectal cancer; Consensus molecular subtypes; IHC; Immunohistochemistry; Online classification tool.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis*
  • CDX2 Transcription Factor / analysis
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • Cytoskeletal Proteins / analysis
  • Humans
  • Image Processing, Computer-Assisted / methods*
  • Immunohistochemistry / instrumentation
  • Immunohistochemistry / methods*
  • Internet
  • Membrane Proteins / analysis
  • Microsatellite Instability*
  • Microscopy / instrumentation
  • Microscopy / methods
  • Receptor, Serotonin, 5-HT2B / analysis
  • Zinc Finger E-box-Binding Homeobox 1 / analysis


  • Biomarkers, Tumor
  • CDX2 Transcription Factor
  • CDX2 protein, human
  • Cytoskeletal Proteins
  • FRMD6 protein, human
  • HTR2B protein, human
  • Membrane Proteins
  • Receptor, Serotonin, 5-HT2B
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1