Fibroblast Growth Factor Receptor 1 Gene Copy Number and mRNA Expression in Primary Colorectal Cancer and Its Clinicopathologic Correlation

Pathobiology. 2015;82(2):76-83. doi: 10.1159/000398807. Epub 2015 Jun 16.

Abstract

Objectives: Fibroblast growth factor receptor 1 (FGFR1) has been reported to be overexpressed in colorectal cancer (CRC) and suggested to be a therapeutic target. In this study, we investigated FGFR1 expression and amplification in CRC and its correlation with clinicopathologic parameters.

Methods: FGFR1 dual-color fluorescence in situ hybridization and mRNA in situ hybridization were performed on tissue array blocks composed of 291 consecutive primary CRCs.

Results: Of the 291 CRC cases, FGFR1 gene amplification was found in 11 (3.8%) cases, high FGFR1 polysomy in 4 (1.4%) cases, and FGFR1 gene copy number (GCN) gain (GCN >2) in 77 (26.5%) cases. FGFR1 GCN gain was significantly associated with left-sided location, lymph node metastasis, distant metastasis, and higher TNM stage (p < 0.05). FGFR1 GCN gain also correlated with poor patient survival (p = 0.015). FGFR1 mRNA overexpression (score 3-4) was present in 11.7% (34/291) of the patients and was significantly associated with FGFR1 GCN alteration (Pearson correlation coefficient, r = 0.463; p < 0.001).

Conclusion: FGFR1 GCN gain was more frequently found (26.5%) than gene amplification (3.8%) and correlated with aggressive clinical behavior in consecutive CRC patients. FGFR1 GCN alteration was associated with a high FGFR1 mRNA level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / physiopathology*
  • Female
  • Gene Amplification
  • Gene Dosage*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Prognosis
  • RNA, Messenger / genetics*
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics*
  • Survival Analysis
  • Tissue Array Analysis

Substances

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