FGFR1 is an adverse outcome indicator for luminal A breast cancers

Oncotarget. 2016 Jan 26;7(4):5063-73. doi: 10.18632/oncotarget.6563.

Abstract

Fibroblast growth factor receptor 1 (FGFR1) has been suggested to be the candidate gene for 8p11-12 amplification in breast cancer and its therapeutic/ prognostic value is explored. Most previous studies focused on FGFR1 gene amplification, which may not necessarily lead to protein expression. Therefore, analysis of protein level may have more clinical relevance. We evaluated FGFR1 expression in a large cohort of breast cancer by immunohistochemistry, correlated with the tumor clinic-pathologic features, biomarkers expression, and patient's survival. FGFR1 expression was associated mainly with luminal cancers, particularly luminal B subtype (23.5%; p < 0.001), and it also showed adverse prognostic impact on luminal A cancers. FGFR1 expression was associated with higher pN (p = 0.023), pT (p = 0.003) stages, lymphovascular invasion (p = 0.010), p-cadherin (p = 0.028), synaptophysin (p = 0.009) and SOX2 expression (p = 0.034) in luminal A cancers. FGFR1 expressing luminal A cancers showed a similar outcome as luminal B cancers. Multivariate Cox regression analysis demonstrated FGFR1 positive luminal A cancers to be an independently poor prognosticator for disease free survival in luminal cancers (hazard ratio = 3.341, p = 0.008). Thus FGFR1 could be useful in identifying the aggressive cases amongst heterogeneous luminal A cancers. Given the relevance of FGFR pathway in treatment resistance in luminal cancers, FGFR1 could be an important tumor biomarker and adverse prognostic factor potentially exploitable in the clinical management of luminal cancers.

Keywords: breast cancer; fibroblast growth factor receptor 1; immunohistochemistry; luminal subtype.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Gene Amplification
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prognosis
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics*
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism*
  • Survival Rate
  • Tissue Array Analysis

Substances

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