Immunohistochemical Localization of Wild-type EGFR, E746-A750 Frame Deletion in Exon 19, and L858R Point Mutation in Exon 21 in Triple-negative Breast Cancer

Appl Immunohistochem Mol Morphol. 2015 Oct;23(9):653-60. doi: 10.1097/PAI.0000000000000127.

Abstract

Aim: This study evaluated wild-type EGFR, E746-A750 frame deletion in exon 19, and L858R point mutation in exon 21 by immunohistochemistry in patients with triple-negative breast cancer (TNBC).

Methods: A retrospective study included 99 untreated early-stage and advanced-stage TNBC patients. Immunohistochemical localization of wild-type EGFR, EGFR E746-A750 deletion in exon 19, and EGFR L858R mutation in exon 21 was performed on formalin-fixed paraffin-embedded tissue blocks using mutation-specific primary antibodies.

Results: EGFR protein expression was noted in 27% (27/99) of patients with 2+ or 3+ staining intensity in 7% (7/99) of patients. Significant correlation of EGFR protein expression with subgroups of clinicopathologic parameters was not found. In univariate and multivariate survival analysis, high EGFR expression (2+ or 3+) emerged as a significant prognostic factor for disease-free survival. With respect to mutation status, exon 19 deletion was observed in 3% (3/99) of patients. One patient with exon 19 deletion having high EGFR protein (2+) expression developed lung metastasis, whereas the other 2 patients with exon 19 deletion had low EGFR protein (1+) expression and remained disease free during the study period.

Conclusions: EGFR protein overexpression was observed in one fourth of TNBCs with very low incidence of EGFR-activating mutations in patients of western India.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Base Sequence*
  • DNA Mutational Analysis
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Exons
  • Female
  • Gene Expression
  • Genotype
  • Humans
  • Immunohistochemistry
  • India
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / secondary
  • Middle Aged
  • Molecular Sequence Data
  • Neoplasm Staging
  • Point Mutation*
  • Retrospective Studies
  • Sequence Deletion*
  • Survival Analysis
  • Triple Negative Breast Neoplasms / diagnosis
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / mortality
  • Triple Negative Breast Neoplasms / pathology

Substances

  • EGFR protein, human
  • ErbB Receptors