Use of monoclonal antibodies to detect specific mutations in formalin-fixed, paraffin-embedded tissue sections

Hum Pathol. 2016 Jul:53:168-77. doi: 10.1016/j.humpath.2016.03.013. Epub 2016 Apr 13.

Abstract

Treatment options for cancer patients have changed considerably in recent years with the introduction of variable gene mutation and targeted therapy. Although molecular testing for gene mutations remains the gold standard in assessing biopsy tissues for specific mutations and for subsequent therapy, recent developments have led to the use of highly specific monoclonal antibodies to detect mutated genes in tissue sections. Some of the early developments included antibodies against EGFR, but have expanded to include antibodies detecting mutated RAS, BRAF, and SDHx. Immunohistochemical detection of gene mutations using mutation-specific antibodies has the advantage of allowing the detailed visualization of protein distributions in situ and provides direct visualization of the heterogeneity in the distribution of targeted proteins. This review will discuss the use of selected mainly monoclonal antibodies targeting specific mutated molecules and indicate how the detection of these proteins can be used for chemotherapeutic purposes in targeting mutated genes.

Keywords: BRAF; EGFR; Gene sequencing; Immunohistochemistry; Mutation-specific antibodies; SDHB.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal / immunology*
  • Antibody Specificity
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / immunology
  • DNA Mutational Analysis / methods*
  • Fixatives*
  • Formaldehyde*
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry*
  • Mutation*
  • Neoplasms / genetics*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Paraffin Embedding*
  • Phenotype
  • Predictive Value of Tests
  • Reproducibility of Results
  • Tissue Fixation / methods*

Substances

  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • Fixatives
  • Formaldehyde