Pulmonary adenocarcinoma with enteric differentiation: Dissecting oncogenic genes alterations with DNA sequencing and FISH analysis

Exp Mol Pathol. 2017 Apr;102(2):276-279. doi: 10.1016/j.yexmp.2017.02.014. Epub 2017 Feb 22.


Background: Pulmonary Adenocarcinoma with Enteric Differentiation (PAED) is a rare subtype of adenocarcinoma of emerging interest, recently introduced in the 2015 WHO classification. However, little is known about major molecular signatures of this class of adenocarcinomas and information about new biomarkers totally lack.

Methods: We examined the NRAS, PIK3CA, EGFR, KRAS and BRAF status through mass spectrometry sequencing and ALK rearrangement by FISH in a series of 8 PAEDs.

Results: 1/8 (12.5%) case had a simultaneous PIK3CA mutation (E545K) and an EML4-ALK translocation. KRAS gene showed a mutation in the codon 12 in 4/8 of PAED (50%), NRAS, BRAF and EGFR genes were wild type in all tumor samples.

Conclusions: We concluded that PIK3CA mutations and ALK rearrangement occur also in PAEDs, while NRAS mutations might be a very rare event similarly to pulmonary adenocarcinomas of conventional type. KRAS is the prevailing gene mutated in this class of adenocarcinoma.

Keywords: ALK; EGFR; Enteric; K-RAS; Lung adenocarcinoma; PIK3CA.

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / genetics*
  • Adenocarcinoma of Lung
  • Aged
  • Anaplastic Lymphoma Kinase
  • Class I Phosphatidylinositol 3-Kinases
  • Codon
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Female
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism
  • Gene Expression Regulation, Neoplastic
  • Gene Rearrangement*
  • Humans
  • In Situ Hybridization, Fluorescence*
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Middle Aged
  • Mutation
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Sequence Analysis, DNA*


  • Codon
  • KRAS protein, human
  • Membrane Proteins
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases
  • GTP Phosphohydrolases
  • NRAS protein, human
  • Proto-Oncogene Proteins p21(ras)