Genotyping and Immunohistochemistry of Gastrointestinal Stromal Tumors: An Update

Semin Diagn Pathol. 2015 Sep;32(5):392-9. doi: 10.1053/j.semdp.2015.02.017. Epub 2015 Feb 7.

Abstract

Gastrointestinal stromal tumors (GISTs) were originally thought to harbor either KIT or platelet-derived growth factor receptor A (PDGFRA) mutations only. However, more recent discoveries have highlighted additional, less common oncogenic driver mutations including NF1, BRAF, and succinate dehydrogenase (SDH) mutations. Genotyping GISTs has become more important since not all genotypes respond equally to FDA-approved tyrosine kinase inhibitors. GIST is a paradigm for personalized cancer therapy. Recent studies demonstrate how immunohistochemistry can be used both to diagnose GIST and to screen for specific mutations. DOG1 is particularly useful in the diagnosis of KIT-negative GIST, including tumors with PDGFRA mutations, which can also potentially be identified by immunohistochemistry for PDGFRA. SDHB immunohistochemistry is useful in characterizing GISTs with SDHA-D mutations, whereas SDHA immunohistochemistry is able to identify SDHA mutant GISTs.

Keywords: BRAF; GIST; KIT; NF1; Platelet-derived growth factor receptor A; Succinate Dehydrogenase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Gastrointestinal Neoplasms / chemistry
  • Gastrointestinal Neoplasms / genetics*
  • Gastrointestinal Neoplasms / pathology
  • Gastrointestinal Stromal Tumors / chemistry
  • Gastrointestinal Stromal Tumors / genetics*
  • Gastrointestinal Stromal Tumors / pathology
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry*
  • Molecular Diagnostic Techniques
  • Mutation
  • Neoplasm Proteins / genetics*
  • Phenotype
  • Predictive Value of Tests
  • Prognosis

Substances

  • Biomarkers, Tumor
  • Neoplasm Proteins