title: Serum angiopoietin-2 and soluble VEGFR-2 levels predict malignancy of ovarian neoplasm and poor prognosis in epithelial ovarian cancer.
abstract: BACKGROUND
  The aim of the study was to explore the serum levels of eight angiogenesis biomarkers in patients with benign, borderline or malignant epithelial ovarian neoplasms and to compare them to those of healthy controls. In addition, we aimed to study how those biomarkers predict the clinical course and survival of patients with epithelial ovarian cancer.
  
  
  METHODS
  We enrolled 132 patients with ovarian neoplasms and 32 unaffected women in this study. Serum samples were collected preoperatively at the time of diagnosis and the levels of angiogenesis biomarkers were measured with an ELISA.
  
  
  RESULTS
  Levels of Ang-1, Ang-2, VEGF, VEGF-D, VEGF/sVEGFR-2 and Ang-2/ sVEGFR-2 ratios were elevated whereas sVEGFR-2 was lower in patients with ovarian carcinoma than in women with normal ovaries, benign and/or borderline ovarian neoplasms. In ROC analysis, the area under the curve for serum Ang-2/sVEGFR-2 ratio (0.76) was greater than Ang-2 (0.75) and VEGF (0.65) but lower than for CA 125 (0.90) to differentiate ovarian cancer from benign or borderline ovarian tumors. In ovarian cancer high Ang-2/sVEGFR-2 ratio was associated with the presence of ascites, high stage and grade of ovarian cancer, with the size of primary residual tumor>1 cm and with recurrence of disease. Elevated Ang-2, VEGF, VEGF/sVEGFR-2, Ang-2/VEGF and Ang-2/sVEGFR-2 ratios and low level of sVEGFR-2 were significant predictors of poor overall survival (OS) and recurrence free survival (RFS) in univariate survival analyses.
  
  
  CONCLUSIONS
  Ovarian cancer patients had elevated levels of angiogenesis related growth factors in circulation reflecting increased angiogenesis and poor prognosis. The serum level of Ang-2 predicted most accurately poor OS and Ang-2/sVEGFR-2 ratio malignancy of ovarian neoplasms and short RFS.
authors.forename: Hanna
authors.initials: H
authors.lastname: Sallinen
authors.forename: Tommi
authors.initials: T
authors.lastname: Heikura
authors.forename: Jonna
authors.initials: J
authors.lastname: Koponen
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kosma
authors.forename: Seppo
authors.initials: S
authors.lastname: Heinonen
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
authors.affiliation: Department of Gynecology, Kuopio University Hospital, P,O, Box 900, Kuopio, FIN 70029 KYS, Finland. Maarit.Anttila@kuh.fi.
authors.forename: Maarit
authors.initials: M
authors.lastname: Anttila
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042702:Angiopoietin-2 / Q000097:blood*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D018394:CA-125 Antigen / Q000097:blood; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000401:mortality / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000097:blood; D010051:Ovarian Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood*; D055815:Young Adult
chemical_list: D042702:Angiopoietin-2; D015415:Biomarkers; D018394:CA-125 Antigen; D040301:Vascular Endothelial Growth Factor Receptor-2