Epidermal growth factor receptor mutations in adenocarcinoma in situ and minimally invasive adenocarcinoma detected using mutation-specific monoclonal antibodies

Lung Cancer. 2016 Sep:99:143-7. doi: 10.1016/j.lungcan.2016.07.009. Epub 2016 Jul 12.

Abstract

Objectives: Epidermal growth factor receptor (EGFR) mutation rates in adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) were studied using both DNA analysis and mutation-specific immunohistochemistry.

Materials and methods: The peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method was used to detect mutations in exons 18, 19, 20, and 21 of the EGFR gene in DNA samples extracted from paraffin-embedded tissue sections. Simultaneously, immunohistochemical analysis with two EGFR mutation-specific monoclonal antibodies was used to identify proteins resulting from an in-frame deletion in exon 19 (E746_A750del) and a point mutation replacing leucine with arginine at codon 858 of exon 21 (L858R).

Results: Forty-three tumors (22 AIS and 21 MIA) were examined. The EGFR mutation rate in AIS detected by DNA analysis was 27.3% (L858R, 5/22; exon 19 deletion,1/22), whereas that detected in MIA was 42.9% (L858R,4/21; exon 19 deletion,5/21). Mutations detected by immunohistochemical analysis included 22.7% (L858R, 4/22; exon 19 deletion, 1/22) in AIS and 42.9% (L858R, 4/21; exon 19 deletion, 5/21) in MIA. Although some results were contradictory, concordant results were obtained using both assays in 38 of 43 cases (88.4%).

Conclusion: DNA and immunohistochemical analyses revealed similar EGFR mutation rates in both MIA and AIS, suggesting that mutation-specific monoclonal antibodies are useful to confirm DNA assay results.

Keywords: Early adenocarcinoma; Epidermal growth factor receptor mutation; Immunohistochemistry; Lung cancer; Subtype.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology*
  • Adenocarcinoma in Situ / genetics*
  • Adenocarcinoma in Situ / pathology*
  • Aged
  • Antibodies, Monoclonal
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Immunohistochemistry* / methods
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Invasiveness
  • Neoplasm Staging

Substances

  • Antibodies, Monoclonal
  • ErbB Receptors