Expression of the angopoietin-1, angopoietin-2, Tie2, and vascular endothelial growth factor gene in epithelial ovarian cancer

Gynecol Oncol. 2004 Apr;93(1):215-22. doi: 10.1016/j.ygyno.2003.12.031.


Objectives: Angiopoietin/Tie2 system with vascular endothelial growth factor (VEFG) is known to be important for the initiation of angiogenesis in tumors. The aim was to evaluate whether angiopoietin/Tie2 system with VEFG affects prognosis in patients of epithelial ovarian cancer.

Methods: Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), Tie2, and VEGF gene expression were analyzed by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) in 85 epithelial ovarian cancer surgical specimens. These gene expressions were correlated with clinical-pathological parameters, microvessel density (MVD), and patients' survival.

Results: Ang-1/Ang-2 gene expression ratio, VEGF, and Tie2 gene expression significantly associated with MVD, respectively (P < 0.0001, P = 0.024, P = 0.005). The patients with low Ang-1/Ang-2 gene expression ratio and high VEGF gene expression were found to have a significantly higher MVD when compared to others (P = 0.0003). Moreover, there was a significant difference between the values of MVD in patients with low Ang-1/Ang-2 gene expression ratio and high VEGF and high Tie2 gene expression and those in others (P = 0.0025). FIGO stage (P = 0.014), residual disease (P = 0.042), histological grade (P = 0.028), Ang-1/Ang-2 gene expression ratio (P = 0.010), and combination of Ang-1/Ang-2 gene expression ratio and VEGF gene expression (P = 0.019), were found to be significantly associated with a poor prognosis in univariate Cox regression analysis. Multivariate Cox regression analysis revealed that FIGO stage is an independent prognostic factor (P = 0.035). Low Ang-1/Ang-2 gene expression ratio had a tendency to be an independent prognostic factor (P = 0.061).

Conclusions: Angiogenesis occurred by angiopoietin/Tie2 system in concert with VEGF in epithelial ovarian cancer did not affect patients' survival. However, gene expression of Ang-1 and Ang-2 might present a pertinent diagnostic tool to select a high-risk group of patients independent of clinical-pathological parameters and a new insight to understand the biology of epithelial ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-1 / biosynthesis*
  • Angiopoietin-1 / genetics
  • Angiopoietin-2 / biosynthesis*
  • Angiopoietin-2 / genetics
  • Female
  • Gene Expression
  • Humans
  • Middle Aged
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism*
  • Ovarian Neoplasms / blood supply
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Prognosis
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptor, TIE-2 / biosynthesis*
  • Receptor, TIE-2 / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vascular Endothelial Growth Factor A / biosynthesis*
  • Vascular Endothelial Growth Factor A / genetics


  • ANGPT1 protein, human
  • Angiopoietin-1
  • Angiopoietin-2
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Receptor, TIE-2