ALK, ROS1 and RET fusions in 1139 lung adenocarcinomas: a comprehensive study of common and fusion pattern-specific clinicopathologic, histologic and cytologic features

Lung Cancer. 2014 May;84(2):121-6. doi: 10.1016/j.lungcan.2014.02.007. Epub 2014 Feb 19.


Background: To have a comprehensive investigation of the clinicopathologic, histologic and cytologic features of fusion-positive lung adenocarcinomas.

Methods: Quantitative real-time reverse transcriptase PCR (qRT-PCR) and reverse transcriptase PCR (RT-PCR) were simultaneously performed to screen ALK, ROS1 and RET fusions in resected tumor samples from 1139 Chinese lung adenocarcinoma patients, with validation of positive results using fluorescent in situ hybridization. Clinicopathologic characteristics, predominant histologic subtype and cytomorphology were assessed in fusion-positive lung adenocarcinomas and compared to those harboring EGFR, KRAS, HER2 or BRAF mutations.

Results: There were 58 (5.1%) ALK fusions, 11 (1.0%) ROS1 fusions and 15 (1.3%) RET fusions. Tumors with ROS1 fusions had significantly larger diameter than ROS1 fusion-negative tumors (P = 0.007), whereas all the 15 tumors harboring RET fusions were ≤ 3 cm in diameter (P = 0.001). The three fusion genes were all more prevalent in solid-predominant adenocarcinoma. Compared to fusion-negative lung adenocarcinomas, tumors harboring a fusion gene had significantly higher prevalence of extracellular mucin (P < 0.001), cribriform pattern (P < 0.001), signet ring cells (P < 0.001) and hepatoid cytology (P < 0.001). No significant difference in relapse-free survival (P = 0.147) and overall survival (P = 0.444) was observed between fusion-positive and fusion-negative patients.

Conclusions: This study showed fusion-positive lung adenocarcinomas had identifiable common and fusion-pattern specific clinicopathologic, histologic and cytologic features, offering implications for fusion genes screening.

Keywords: ALK fusions; Cytomorphology; Histology; Lung adenocarcinoma; RET fusions; ROS1 fusions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Anaplastic Lymphoma Kinase
  • DNA Mutational Analysis
  • Disease-Free Survival
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics*
  • Protein-Tyrosine Kinases / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins c-ret / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor, ErbB-2 / genetics
  • ras Proteins / genetics


  • KRAS protein, human
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ERBB2 protein, human
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • ROS1 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, ErbB-2
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins