Molecular analysis of peripheral non-squamous non-small cell lung cancer sampled by radial EBUS

Respirology. 2016 May;21(4):718-26. doi: 10.1111/resp.12737. Epub 2016 Jan 27.

Abstract

Background and objective: Treatment optimization of non-squamous non-small-cell lung cancers (nonSq-NSCLC) relies on the molecular analysis of the tumour. We aimed to assess the predictive factors of molecular analysis feasibility (MAF) from samples of peripheral nonSq-NSCLC obtained by radial endobronchial ultrasound bronchoscopy (r-EBUS) and 1.5 mm microbiopsy forceps.

Methods: We reviewed data from consecutive peripheral lung nodules sampled with r-EBUS between January 2012 and July 2014 at a single French University Hospital. nonSq-NSCLC were systematically analysed for EGFR, KRAS, ALK, HER2, PI3K and BRAF throughout the study, and c-MET and ROS1 alterations for the last 10 months.

Results: Of 111 nonSq-NSCLC diagnosed by r-EBUS (113 procedures, mean nodule diameter 28 ± 15 mm), 88 were analysed for EGFR and ALK, 87 for KRAS, 86 for HER2, PI3K and BRAF and 14 for c-MET. Forty-one mutations were identified (23 KRAS, 10 EGFR, 2 BRAF, 1 HER2 and 5 ALK rearrangements). Four c-MET overexpressions were noted. MAF rose from 67% for the first 57 procedures to 89% for the last 56 procedures (P = 0.02) likely due to a higher number of biopsies performed (2 ± 1 vs 3 ± 2, P = 0.005). Upper or middle lobe location (OR 1.19, 95% CI: 1.02-1.38, P = 0.03), and at least three biopsies (OR 1.20, 95% CI: 1.04-1.40, P = 0.02) were predictive factors of MAF. Percentage of tumour cells, size of lesion and distance to the pleura did not correlate with MAF.

Conclusion: Multi-gene molecular analysis could be performed in nearly 80% of paraffin-embedded biopsies or smear specimens sampled by r-EBUS assisted bronchoscopy of peripheral tumoral lung nodules.

Keywords: lung adenocarcinoma; molecular analysis; navigational bronchoscopy; peripheral lung nodule; radial endobronchial-ultrasound bronchoscopy.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anaplastic Lymphoma Kinase
  • Biopsy
  • Bronchoscopy / instrumentation
  • Bronchoscopy / methods*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • ErbB Receptors / genetics
  • Female
  • Gene Rearrangement
  • Humans
  • Lung / pathology*
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Mutation
  • Phosphatidylinositol 3-Kinases / genetics
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor, ErbB-2 / genetics
  • Ultrasonography, Interventional / methods

Substances

  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Phosphatidylinositol 3-Kinases
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-met
  • ROS1 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, ErbB-2
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)