Expression of the angopoietin-1, angopoietin-2, Tie2, and vascular endothelial growth factor gene in epithelial ovarian cancer.
OBJECTIVE
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.
Hata
Kohkichi
K
Department of Obstetrics and Gynecology, University School of Medicine, Izumo 693-8501, Japan. hata3@med.shimane-u.ac.jp
Nakayama
Kentaro
K
Fujiwaki
Ritsuto
R
Katabuchi
Hidetaka
H
Okamura
Hitoshi
H
Miyazaki
Kohji
K
D042683:Angiopoietin-1 / Q000096:biosynthesis* / Q000235:genetics; D042702:Angiopoietin-2 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D042787:Receptor, TIE-2 / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2