Preoperative angiopoietin-2 serum levels: a marker of malignant potential in ovarian neoplasms and poor prognosis in epithelial ovarian cancer.
BACKGROUND
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.
Department of Molecular Medicine, University of Eastern Finland, Department of Gynaecology and Obstetrics, Kuopio University Hospital, Kuopio, Finland.
Hanna
H
Sallinen
Tommi
T
Heikura
Svetlana
S
Laidinen
Veli-Matti
VM
Kosma
Seppo
S
Heinonen
Seppo
S
Ylä-Herttuala
Maarit
M
Anttila
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042683:Angiopoietin-1 / Q000032:analysis / Q000097:blood; D042702:Angiopoietin-2 / Q000032:analysis / Q000097:blood*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood; D002277:Carcinoma / Q000097:blood / Q000175:diagnosis* / Q000401:mortality / Q000601:surgery; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods*; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000175:diagnosis / Q000401:mortality / Q000601:surgery; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000401:mortality / Q000601:surgery; D057234:Preoperative Period; D011379:Prognosis; D016019:Survival Analysis; D055815:Young Adult
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D014408:Biomarkers, Tumor