No evidence for BRAF-V600E mutations in gastroeosophageal tumors: results from a high-throughput analysis of 534 cases using a mutation-specific antibody

Appl Immunohistochem Mol Morphol. 2013 Oct;21(5):426-30. doi: 10.1097/PAI.0b013e31827ce693.

Abstract

Background: BRAF-V600E mutations are found in a broad spectrum of cancer types and can be successfully targeted by specific therapeutic compounds. Little data on the prevalence of BRAF-V600E mutations in tumors of the upper gastrointestinal tract are available.

Materials and methods: We constructed tissue microarrays of formalin-fixed and paraffin-embedded specimens of 534 gastroesophageal tumors (119 squamous cell cancers and 72 adenocarcinomas of the esophagus, 63 cancers of the gastroesophageal junction/cardia, 199 gastric cancers of the corpus or antrum, 81 gastric gastrointestinal stromal tumors) and performed anti-BRAF-V600E immunostaining using the mutation-specific antibody VE1. As control tissue we used 3 melanoma cases with confirmed BRAF-V600E mutation and distinct VE1 immunostaining.

Results: None of the gastroesophageal tumor cases showed a positive immunostaining signal.

Conclusions: BRAF-V600E mutation is not a relevant oncogenic driver in gastroesophageal tumors. Immunohistochemical analysis using mutation-specific antibodies on tissue microarrays is a feasible, time-efficient and cost-efficient approach to high-throughput screening for specific mutations in large tumor series.

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Aged
  • Antibodies, Monoclonal* / isolation & purification
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Esophageal Neoplasms / diagnosis*
  • Esophageal Neoplasms / pathology
  • Feasibility Studies
  • Female
  • Gastrointestinal Stromal Tumors / diagnosis*
  • Gastrointestinal Stromal Tumors / genetics
  • Gastrointestinal Stromal Tumors / pathology
  • High-Throughput Screening Assays
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mutation / genetics
  • Paraffin Embedding
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / immunology
  • Proto-Oncogene Proteins B-raf / metabolism*
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Tissue Array Analysis

Substances

  • Antibodies, Monoclonal
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf