Characterization of common and rare mutations in EGFR and associated clinicopathological features in a large population of Chinese patients with lung cancer

Pathol Res Pract. 2017 Jul;213(7):749-758. doi: 10.1016/j.prp.2017.04.007. Epub 2017 Apr 20.

Abstract

Lung cancer with EGFR mutation is often associated pathological characteristics and good responses to EGFR tyrosine kinase inhibitors (TKIs). However, certain types of rare EGFR mutations have be linked to cases with poor response to EGFR TKIs. Therefore, extensive molecular screening and pathological characterization are essential for accurate diagnosis and selection of effective treatment plans. Although a large body of studies have established the rate of EGFR mutations as a whole entity, the rates of each individual types of mutations, especially those rare ones, have not been precisely determined in large patient populations with uniform genetic background. To address this issue, we assembled a large cohort of 456 Chinese patients with lung cancers to determine the rate of both common and rare forms of EGFR mutations and associated clinicopathological features in this retrospective study. We have found single or double EGFR mutations in 200 (43.9%) patients, including exon 19 deletions (E19del) (20%), exon 21 L858R (17.1%) and L861Q (1.5%) point mutations, exon 20 T790M (1.3%) and other mutations (1,3%), exon 18 mutations (1.3%), and double mutations (1.3%). EGFR mutation as well as its subtypes E19del, L858R, or double mutations were associated with female patients or never-smokers. In contrast, rare mutations, especially EGFR TKI resistant exon 20 mutations, were not statistically associated with any clinicopathological features, implicating that tumorigenesis driven by different EGFR mutations were mechanistically different. In summary, we have determined occurring rate of EGFR subtype mutations and demonstrated that different mutations showed different clinicopathological manifestations in lung cancer.

Keywords: E19del; EGFR TKI; L858R; L861Q; T790M.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Asian People / genetics
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • China
  • DNA Mutational Analysis
  • ErbB Receptors / analysis
  • ErbB Receptors / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / chemistry
  • Lung Neoplasms / ethnology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation Rate
  • Mutation*
  • Phenotype

Substances

  • Biomarkers, Tumor
  • EGFR protein, human
  • ErbB Receptors