Cytomorphological identification of advanced pulmonary adenocarcinoma harboring KRAS mutation in lymph node fine-needle aspiration specimens: Comparative investigation of adenocarcinoma with KRAS and EGFR mutations

Diagn Cytopathol. 2015 Jul;43(7):539-44. doi: 10.1002/dc.23242. Epub 2014 Nov 26.

Abstract

Background: Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutation in pulmonary adenocarcinoma is clinically important due to its association with resistance to EGFR inhibitors and poor prognosis. To our knowledge, there has not been a comparative study focusing on cytological nuclear features of pulmonary adenocarcinoma harboring KRAS mutation (KRAS-AD). Hence, we compared the cytomorphology of metastatic KRAS-AD and EGFR-positive adenocarcinoma (EGFR-AD) in aspiration specimens from lymph nodes.

Methods: Forty lymph node aspiration specimens from forty KRAS-AD patients were collected at Samsung Medical Center (Seoul, Korea) from 2009 to 2013. As a control group, 40 EBUS-FNA lymph node specimens from 20 EGFR-AD patients were collected. EGFR-AD specimens were evaluated at Samsung Medical Center (Seoul, Korea) from 2012 to 2013. All 80 specimens were histologically confirmed to metastatic adenocarcinoma. Two pathologists performed a blinded review of all specimens.

Results: Compared with EGFR-AD, KRAS-AD exhibited more severe nuclear pleomorphism (P < 0.001), coarse chromatin (P = 0.001), cherry-red nucleoli (P < 0.001) and naked tumor cells (P = 0.002) with necrotic (P < 0.001) and neutrophilic (P = 0.008) background.

Conclusions: Our study provides the first demonstration of cytomorphologic differentiation between metastatic KRAS-AD and metastatic EGFR-AD in lymph node aspiration specimens.

Keywords: EGFR gene; KRAS gene; adenocarcinoma; endoscopic ultrasound-guided fine needle aspiration; lung.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Aged
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Biopsy, Fine-Needle / methods
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mutation
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Proto-Oncogene Proteins p21(ras) / metabolism

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)