Clinical significance of fibroblast growth factor receptor 2 expression in patients with residual rectal cancer after preoperative chemoradiotherapy: relationship with KRAS or BRAF mutations and MSI status

Tumour Biol. 2016 Aug;37(8):10209-18. doi: 10.1007/s13277-016-4899-z. Epub 2016 Jan 30.

Abstract

This study was designed to determine the prognostic impact and clinical significance of FGFR2 in residual disease after preoperative chemoradiotherapy (CRT) in patients with rectal cancer. The surgical specimens of 145 patients with residual rectal cancer after preoperative CRT were analyzed. To evaluate FGFR2 expression, immunohistochemistry was performed on whole section tissues. KRAS exon 2 (codon 12 and 13), BRAF V600E mutational status, and microsatellite instability (MSI) were determined using polymerase chain reactions. Of the eligible 141 patients, FGFR2 over-expression was observed in 75.9 % (n = 107) and was correlated with perineural invasion (P = 0.005) and inferior tumor regression grading (TRG) (P = 0.009). However, FGFR2 expression had no relationship with KRAS and BRAF mutation results or with MSI results. On univariate analysis, FGFR2 over-expression was significantly associated with worse rectal cancer-specific survival (RCSS) (P = 0.005) and disease-free survival (DFS) (P = 0.035). However, multivariate analysis revealed that FGFR2 over-expression was not independently associated with RCSS and DFS (all P > 0.05). Although FGFR2 over-expression did not independently influence patient outcome, FGFR2 over-expression was associated with worse prognosis and inferior TRG. Our data may aid in understanding the therapeutic approaches targeting FGFR2 in patients with residual rectal cancer after preoperative CRT.

Keywords: Fibroblast growth factor receptor 2; KRAS; Microsatellite instability; Preoperative chemoradiotherapy; Prognosis; Rectal cancer.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Chemoradiotherapy, Adjuvant
  • DNA Mutational Analysis
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Mutation
  • Neoadjuvant Therapy
  • Neoplasm, Residual
  • Polymerase Chain Reaction
  • Prognosis
  • Proportional Hazards Models
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Receptor, Fibroblast Growth Factor, Type 2 / biosynthesis*
  • Rectal Neoplasms / genetics
  • Rectal Neoplasms / metabolism
  • Rectal Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • FGFR2 protein, human
  • Receptor, Fibroblast Growth Factor, Type 2
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)