Skip Navigation LinksHome > December 2010 - Volume 20 - Issue 9 > Preoperative Angiopoietin-2 Serum Levels: A Marker of Malign...
International Journal of Gynecological Cancer:
doi: 10.1111/IGC.0b013e3181f936e3
Ovarian Cancer

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

Sallinen, Hanna MD*†‡; Heikura, Tommi MSc*; Laidinen, Svetlana DVM*; Kosma, Veli-Matti MD, PhD†§; Heinonen, Seppo MD, PhD†‡; Ylä-Herttuala, Seppo MD, PhD*; Anttila, Maarit MD, PhD*†‡

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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.

Copyright © 2010 by IGCS and ESGO

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