Associations Between Hepatocyte Growth Factor, c-Met, and Basic Fibroblast Growth Factor and Survival in Endometrial Cancer Patients

Br J Cancer. 2012 Jun 5;106(12):2004-9. doi: 10.1038/bjc.2012.200. Epub 2012 May 22.

Abstract

Background: Hepatocyte growth factor (HGF), c-Met, and basic fibroblast growth factor (bFGF) are molecular markers that contribute to angiogenesis and proliferation in numerous cancers. We assessed the prognostic significance of these factors in tumour and stroma of endometrial cancer (EC) patients (n=211).

Methods: Immunohistochemistry (IHC) was used to detect tumour and stromal protein expression of the biomarkers. Associations between expression and clinicopathological factors were assessed using Chi-square tests. Kaplan-Meier curves, log-rank tests, and Cox regression were used to summarise associations between biomarker expression and overall survival (OS) and recurrence-free survival (RFS).

Results: Tumour bFGF was significantly associated with high-grade endometrioid and clear cell histology (P<0.001), advanced stage (P=0.008), positive lymph-node involvement (P=0.002), poor OS (log-rank test, P=0.009), and poor RFS (P<0.001). In multivariable analyses, cases with HGF-positive, stromal bFGF-positive tumours had a lower risk of death compared with cases with HGF-positive, stromal bFGF-negative tumours (hazard ratio (HR): 0.14, 95% CI: 0.03, 0.60). Cases with HGF-positive, bFGF-positive tumours had a higher risk of recurrence compared with cases with negative expression of both markers (HR: 9.88, 95% CI: 2.63, 37.16).

Conclusion: These IHC data show that tumour and stromal bFGF expression have opposite associations with survival outcomes in EC patients. If confirmed in larger studies, tumour-derived bFGF could be an attractive target in EC therapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Disease-Free Survival
  • Endometrial Neoplasms / metabolism*
  • Endometrial Neoplasms / mortality
  • Endometrial Neoplasms / pathology
  • Female
  • Fibroblast Growth Factor 2 / metabolism*
  • Hepatocyte Growth Factor / biosynthesis*
  • Humans
  • Middle Aged
  • Prognosis

Substances

  • Biomarkers, Tumor
  • Fibroblast Growth Factor 2
  • Hepatocyte Growth Factor