The clinical relevance of pathologic subtypes in metastatic lung adenocarcinoma

J Thorac Oncol. 2014 May;9(5):654-63. doi: 10.1097/JTO.0000000000000150.


Introduction: The International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of lung adenocarcinoma recommends identification of pathologic patterns in metastatic samples where possible. We investigated the clinical relevance of these patterns.

Methods: Patients with a surgical biopsy of lung adenocarcinoma from a metastatic site were included. Slides were reviewed by an anatomical pathologist identifying the histologic patterns of solid with mucin, acinar, micropapillary, papillary, and assigning a major adenocarcinoma subtype according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. EGFR and KRAS mutation testing were performed on formalin-fixed, paraffin-embedded blocks. Mutations were detected by high resolution melting assay with high resolution melting-positive samples confirmed by Sanger sequencing.

Results: One-hundred patients were included. The major histologic subtype prevalence was as follows: solid (50), acinar (29), micropapillary (20), and papillary (1). Of 100 patients, 45 received no systemic therapy with no overall survival differences seen by histologic subtype and 55 received systemic therapy (chemoradiotherapy with curative intent or palliative chemotherapy). Worse survival was seen in the major solid histologic subtype compared with major acinar (hazard ratio 0.32 [95% confidence interval 0.15-0.68], p = 0.003) and micropapillary subtypes (hazard ratio 0.34 [95% confidence interval, 0.17-0.69], p = 0.003). The major solid histologic subtype was less likely to harbor EGFR mutations (p = 0.006) and was less frequent in never smokers (p = 0.010) compared with other histologic subtypes.

Conclusion: The major solid histologic subtype of lung adenocarcinoma at metastatic sites is associated with shorter overall survival on systemic anticancer therapy. Furthermore, the major solid histologic subtype is less likely to harbor EGFR mutations. These results require validation in larger cohorts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / secondary*
  • Adenocarcinoma / therapy
  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology*
  • Bone Neoplasms / secondary
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / secondary
  • DNA Mutational Analysis
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / therapy
  • Male
  • Mediastinal Neoplasms / genetics
  • Mediastinal Neoplasms / pathology*
  • Mediastinal Neoplasms / secondary
  • Middle Aged
  • Pleural Neoplasms / genetics
  • Pleural Neoplasms / pathology*
  • Pleural Neoplasms / secondary
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Survival Rate
  • ras Proteins / genetics


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