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  • Preoperative Angiopoietin-2 Serum Levels: A Marker of Malignant Potential in Ovarian Neoplasms and Poor Prognosis in Epithelial Ovarian Cancer

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Ovarian Cancer
Preoperative Angiopoietin-2 Serum Levels: A Marker of Malignant Potential in Ovarian Neoplasms and Poor Prognosis in Epithelial Ovarian Cancer
  1. Hanna Sallinen, MD*,†,‡,
  2. Tommi Heikura, MSc*,
  3. Svetlana Laidinen, DVM*,
  4. Veli-Matti Kosma, MD, PhD†,§,
  5. Seppo Heinonen, MD, PhD†,‡,
  6. Seppo Ylä-Herttuala, MD, PhD* and
  7. Maarit Anttila, MD, PhD*,†,‡
  1. * Department of Molecular Medicine, A.I.Virtanen Institute,
  2. † Institute of Clinical Medicine, Gynaecology, and Pathology and Forensic Medicine, University of Eastern Finland; Departments of
  3. ‡ Gynaecology and Obstetrics, and
  4. § Pathology, Kuopio University Hospital, Kuopio, Finland.
  1. Address correspondence and reprint requests to Maarit Anttila, MD, PhD, Department of Gynaecology and Obstetrics, Kuopio University Hospital, PO Box 1777, Kuopio, FIN-70211, Finland. E-mail: Maarit.Anttila{at}kuh.fi.

Abstract

Introduction: The aims of the study were to explore the levels of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) in patients with benign, borderline, or malignant epithelial ovarian tumors and to compare them to those of healthy controls. In addition, we aimed to study how Ang-1 and Ang-2 levels predict the clinical course and survival of patients with epithelial ovarian cancer.

Methods: We enrolled 150 patients with ovarian neoplasms and 34 women with healthy ovaries in this study. Furthermore, we measured the levels of Ang-1 and Ang-2 in patients having an ovarian metastasis or another cancer (n = 29). Serum samples were collected preoperatively at the time of diagnosis, and Ang-1 and Ang-2 levels were measured with an enzyme-linked immunosorbent assay.

Results: Angiopoietin-1 and Ang-2 levels were significantly elevated in serum samples of patients with ovarian carcinoma compared with healthy controls (P = 0.0005 and P < 0.0005, respectively). In addition, Ang-2 levels were significantly higher in patients with ovarian carcinoma compared with patients with benign (P < 0.0005) or borderline ovarian tumors (P = 0.011). In receiver operating characteristic analysis, the area under the curve for serum Ang-2 (0.77) was greater than Ang-1 (0.60) but lower than for cancer antigen 125 (0.95) to differentiate ovarian cancer from healthy control. High serum levels of Ang-1 and Ang-2 were associated with primary residual tumor more than 1 cm after debulking surgery, and high Ang-2 levels correlated positively with an advanced tumor stage (P = 0.042). Elevated Ang-2 level (>2.7 ng/mL) was a significant predictor of poor overall and recurrence-free survival (P = 0.043 and P = 0.033, respectively) when assessing Kaplan-Meier curves by a log-rank test.

Conclusions: Patients with ovarian cancer have higher serum levels of angiopoietins than patients with benign or borderline tumors reflecting the increased angiogenesis. These results also suggest that Ang-2 may serve as an angiogenic marker of decreased patient survival in ovarian cancer.

  • Ang-1
  • Ang-2
  • Ovarian carcinoma
  • Endometrial carcinoma
  • Prognosis

https://doi.org/10.1111/IGC.0b013e3181f936e3

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