FGFR4 profile as a prognostic marker in squamous cell carcinoma of the mouth and oropharynx

PLoS One. 2012;7(11):e50747. doi: 10.1371/journal.pone.0050747. Epub 2012 Nov 30.

Abstract

Background: Fibroblast growth factor receptor 4 (FGFR4) is a member of a receptor tyrosine kinase family of enzymes involved in cell cycle control and proliferation. A common single nucleotide polymorphism (SNP) Gly388Arg variant has been associated with increased tumor cell motility and progression of breast cancer, head and neck cancer and soft tissue sarcomas. The present study evaluated the prognostic significance of FGFR4 in oral and oropharynx carcinomas, finding an association of FGFR4 expression and Gly388Arg genotype with tumor onset and prognosis.

Patients and methods: DNA from peripheral blood of 122 patients with oral and oropharyngeal squamous cell carcinomas was used to determine FGFR4 genotype by PCR-RFLP. Protein expression was assessed by immunohistochemistry (IHC) on paraffin-embedded tissue microarrays.

Results: Presence of allele Arg388 was associated with lymphatic embolization and with disease related premature death. In addition, FGFR4 low expression was related with lymph node positivity and premature relapse of disease, as well as disease related death.

Conclusion: Our results propose FGFR4 profile, measured by the Gly388Arg genotype and expression, as a novel marker of prognosis in squamous cell carcinoma of the mouth and oropharynx.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Male
  • Middle Aged
  • Mouth Neoplasms / diagnosis*
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / pathology
  • Oropharyngeal Neoplasms / diagnosis*
  • Oropharyngeal Neoplasms / genetics
  • Oropharyngeal Neoplasms / pathology
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Receptor, Fibroblast Growth Factor, Type 4 / genetics*

Substances

  • Biomarkers, Tumor
  • FGFR4 protein, human
  • Receptor, Fibroblast Growth Factor, Type 4

Grants and funding

This work was supported by FAPESP grants n° 04/15022-0 and n° 04/12054-9 (Fundação de Apoio à Pesquisa de São Paulo, http://www.fapesp.br/). FAPESP is a Research support institution with the sole role of financing peer reviewed projects of the São Paulo State. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.