Angiogenic protein expression in advanced epithelial ovarian cancer.
We set out to determine whether advanced epithelial ovarian cancer (EOC) is associated with elevated serum and ascitic concentrations of the angiogenic factors angiogenin (ANG), basic fibroblastic growth factor (bFGF), and vascular endothelial growth factor (VEGF), and whether the expression of angiogenic factors was associated with tumor vascularity. Serum and ascitic samples were collected from previously untreated patients with FIGO stage III and IV EOC and stored at -70 degreesC. Levels of the three factors were determined by enzyme-linked immunoassay. Histological sections from paraffin blocks of ovarian cancers were stained immunochemically for factor VIII, CD34, and VEGF. Thirty-nine patients were studied, although not all had paired serum and ascitic samples. For each angiogenic factor, the following findings were noted: (a) there was a wide range in serum and ascitic fluid concentrations; (b) the mean serum concentration was higher (P < 0.05) than the mean concentration in normal serum; and (c) the mean serum concentration was lower (P < 0. 05) than the mean ascitic concentration. Overall, the most consistent pattern of elevated serum and ascitic concentrations was with bFGF. With serum samples, 38.9% of patients had a normal VEGF concentration, as did 15.3% for ANG and 7.7% for bFGF. In ascites, the VEGF concentration was in the range for normal serum in 24.5% of samples, compared to 39.4% for ANG and 2.8% for bFGF. In paired samples, both VEGF and bFGF showed higher ascitic concentrations in 100 and 88.3% of samples, compared to 53.3% for ANG. There was no correlation between the serum and/or ascitic concentration of one factor and that of another, suggesting that these factors are independently regulated. Staining with anti-CD34 was more sensitive and reliable than with anti-factor VIII. VEGF staining was most prominent in poorly differentiated tumors and was observed only on tumor cells. There was no correlation between the serum or ascitic concentrations of angiogenic factors and tumor vascularity. Advanced EOC is associated with raised serum and ascitic bFGF concentrations and with markedly elevated ascitic VEGF in most cases. Serum VEGF and serum and ascitic ANG are less often elevated. There was no correlation between the angiogenic profile in serum and ascites and tumor vascularity.
Barton
D P
DP
Division of Gynaecological Oncology and Department of Pathology, St. George's Hospital, London SW170RE, United Kingdom.
Cai
A
A
Wendt
K
K
Young
M
M
Gamero
A
A
De Cesare
S
S
D018952:Antigens, CD34 / Q000032:analysis; D001202:Ascitic Fluid / Q000737:chemistry; D018450:Disease Progression; D016228:Endothelial Growth Factors / Q000032:analysis* / Q000097:blood / Q000235:genetics; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000032:analysis* / Q000097:blood / Q000235:genetics; D006801:Humans; D008222:Lymphokines / Q000032:analysis* / Q000097:blood / Q000235:genetics; D009363:Neoplasm Proteins / Q000032:analysis* / Q000097:blood / Q000235:genetics; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000032:analysis* / Q000235:genetics; D012259:Ribonuclease, Pancreatic; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D018952:Antigens, CD34; D016228:Endothelial Growth Factors; D008222:Lymphokines; D009363:Neoplasm Proteins; D011506:Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; C046366:angiogenin; D012259:Ribonuclease, Pancreatic