Gene status and clinicopathologic characteristics of lung adenocarcinomas with mediastinal lymph node metastasis

Oncotarget. 2016 Sep 27;7(39):63758-63766. doi: 10.18632/oncotarget.11494.

Abstract

Lung cancer with mediastinal lymph node metastasis is more likely to develop recurrence and metastasis after complete resection and targeted therapy is a promising treatment strategy. We performed amplification refractory mutation system (ARMS) fluorescence quantitative PCR to detect the gene status of EGFR, ALK, ROS1 and RET in resected samples from 280 patients who were confirmed to have primary lung adenocarcinomas with N1-N2 lymph node metastasis. Of the 280 patients enrolled, the frequency of EGFR mutations, ALK fusions, ROS1 fusions, RET fusions and no mutations was 42.9%, 10.7%, 1.8%, 3.6% and 42.9%, respectively. Five patients exhibited the coexistence of the EGFR and ALK alterations. ALK, ROS1 and RET fusions were mutually exclusive. The frequency of EGFR mutation was significantly lower among patients with poor differentiation, while the rates of ALK and ROS1 fusions were the opposite. RET fusions also tended to be more prevalent in poorly differentiated patients. EGFR and ALK double positive tumors were characterized by significantly smaller size compared with those had single gene alteration. Our study comprehensively analyzed the distinct and common clinicopathologic characteristics according to genotypes of the cohort, which should help in categorizing patients for efficient screening.

Keywords: ALK; EGFR; RET; ROS1; adenocarcinoma of the lung.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Aged, 80 and over
  • Anaplastic Lymphoma Kinase
  • Cell Differentiation
  • Cohort Studies
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Female
  • Genotype
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Lymphatic Metastasis*
  • Male
  • Mediastinum / pathology*
  • Middle Aged
  • Mutation
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Polymerase Chain Reaction
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-ret / genetics
  • ROC Curve
  • Receptor Protein-Tyrosine Kinases / genetics
  • Sensitivity and Specificity
  • Sex Factors

Substances

  • Proto-Oncogene Proteins
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-ret
  • ROS1 protein, human
  • Receptor Protein-Tyrosine Kinases