Assessment of EGFR and KRAS mutation status from FNAs and core-needle biopsies of non-small cell lung cancer

Cancer Cytopathol. 2015 Apr;123(4):230-6. doi: 10.1002/cncy.21513. Epub 2014 Dec 19.

Abstract

Background: Molecular testing to determine gene mutation status is now the recommended standard of care for patients with advanced or metastatic Non-small cell lung cancer (NSCLC). Because the majority of patients with NSCLC present with metastatic disease, minimally invasive procedures are necessary for diagnosis, staging, and molecular analysis. However, the resulting samples have perceived limitations in the oncology community, and most commercially available tests have not been validated for these sample types. The current study was undertaken to assess the feasibility of determining epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status in fine-needle aspirates (FNAs) and core-needle biopsies (CNBs) after staining with Papanicolaou or hematoxylin and eosin, respectively.

Methods: Gene mutation status was determined in 140 NSCLC tumor samples with proprietary tests for EGFR and KRAS mutations (cobas tests) followed by Sanger sequencing of exons 18 through 21 of the EGFR gene and exon 2 of the KRAS gene. The results were analyzed based on FNA (n = 91) or CNB (n = 49) sampling.

Results: The cobas tests yielded valid results in the majority of FNA and CNB samples for both EGFR (97.9%) and KRAS (93.6%). Moreover, valid results were obtained for 90% of samples that had DNA concentrations below the values recommended by the manufacturer. For samples with valid results from both cobas testing and Sanger sequencing, 95.7% and 93% agreement were observed for EGFR status and KRAS status, respectively.

Conclusions: Gene mutation testing can be successfully performed on cytology and CNB samples, expanding the potential of personalized cancer treatment to patients who have limited tissue samples.

Keywords: cytodiagnosis; fine-needle biopsy; minimally invasive diagnostic procedures; non-small cell lung carcinoma.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy, Fine-Needle
  • Biopsy, Large-Core Needle
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cytological Techniques
  • Early Detection of Cancer / methods
  • Eosine Yellowish-(YS)
  • ErbB Receptors / genetics*
  • Feasibility Studies
  • Female
  • Hematoxylin
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Papanicolaou Test
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Retrospective Studies
  • ras Proteins / genetics*

Substances

  • KRAS protein, human
  • Proto-Oncogene Proteins
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins
  • Eosine Yellowish-(YS)
  • Hematoxylin