Prognostic role of FGFR1 amplification in early-stage non-small cell lung cancer

Br J Cancer. 2014 Jun 10;110(12):2914-22. doi: 10.1038/bjc.2014.229. Epub 2014 May 22.

Abstract

Background: Recently, fibroblast growth factor receptor 1 (FGFR1) was discovered in squamous cell carcinomas (SCC) of the lung with FGFR1 amplification described as a promising predictive marker for anti-FGFR inhibitor treatment. Only few data are available regarding prevalence, prognostic significance and clinico-pathological characteristics of FGFR1-amplified and early-stage non-small cell lung carcinomas (NSCLC). We therefore investigated the FGFR1 gene status in a large number of well-characterised early-stage NSCLC.

Methods: FGFR1 gene status was evaluated using a commercially available fluorescent in situ hybridisation (FISH) probe on a tissue microarray (TMA). This TMA harbours 329 resected, formalin-fixed and paraffin-embedded, nodal-negative NSCLC with a UICC stage I-II. The FISH results were correlated with clinico-pathological features and overall survival (OS).

Results: The prevalence of an FGFR1 amplification was 12.5% (41/329) and was significantly (P<0.0001) higher in squamous cell carcinoma (SCC) (20.7%) than in adenocarcinoma (2.2%) and large cell carcinoma (13%). Multivariate analysis revealed significantly (P=0.0367) worse 5-year OS in patients with an FGFR1-amplified NSCLC.

Conclusions: FGFR1 amplification is common in early-stage SCC of the lung and is an independent and adverse prognostic marker. Its potential role as a predictive marker for targeted therapies or adjuvant treatment needs further investigation.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Disease-Free Survival
  • Female
  • Gene Amplification*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics*
  • Tissue Array Analysis

Substances

  • FGFR1 protein, human
  • Receptor, Fibroblast Growth Factor, Type 1