Clinicopathological Characteristics of RET Rearranged Lung Cancer in European Patients

J Thorac Oncol. 2016 Jan;11(1):122-7. doi: 10.1016/j.jtho.2015.09.016.

Abstract

Introduction: Rearrangements of RET are rare oncogenic events in patients with non-small cell lung cancer (NSCLC). While the characterization of Asian patients suggests a predominance of nonsmokers of young age in this genetically defined lung cancer subgroup, little is known about the characteristics of non-Asian patients. We present the results of an analysis of a European cohort of patients with RET rearranged NSCLC.

Methods: Nine hundred ninety-seven patients with KRAS/EGFR/ALK wildtype lung adenocarcinomas were analyzed using fluorescence in situ hybridization for RET fusions. Tumor specimens were molecularly profiled and clinicopathological characteristics of the patients were collected.

Results: Rearrangements of RET were identified in 22 patients, with a prevalence of 2.2% in the KRAS/EGFR/ALK wildtype subgroup. Co-occurring genetic aberrations were detected in 10 patients, and the majority had mutations in TP53. The median age at diagnosis was 62 years (range, 39-80 years; mean ± SD, 61 ± 11.7 years) with a higher proportion of men (59% versus 41%). There was only a slight predominance of nonsmokers (54.5%) compared to current or former smokers (45.5%).

Conclusions: Patients with RET rearranged adenocarcinomas represent a rare and heterogeneous NSCLC subgroup. In some contrast to published data, we see a high prevalence of current and former smokers in our white RET cohort. The significance of co-occurring aberrations, so far, is unclear.

Keywords: Adenocarcinoma; Clinicopathological characteristics; NSCLC; RET rearrangement; Smoking history; TP53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Europe
  • Female
  • Follow-Up Studies
  • Gene Rearrangement*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Oncogene Proteins, Fusion / genetics
  • Prognosis
  • Proto-Oncogene Proteins c-ret / genetics*
  • Retrospective Studies

Substances

  • Biomarkers, Tumor
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins c-ret
  • RET protein, human