Barton D P, Cai A, Wendt K, Young M, Gamero A, De Cesare S
Division of Gynaecological Oncology and Department of Pathology, St. George's Hospital, London SW170RE, United Kingdom.
Clin Cancer Res. 1997 Sep;3(9):1579-86.
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.
我们着手确定晚期上皮性卵巢癌（EOC）是否与血管生成因子血管生成素（ANG）、碱性成纤维细胞生长因子（bFGF）和血管内皮生长因子（VEGF）的血清及腹水中浓度升高有关，以及血管生成因子的表达是否与肿瘤血管形成有关。收集了FIGO III期和IV期未经治疗的EOC患者的血清和腹水样本，并储存于-70℃。通过酶联免疫吸附测定法测定这三种因子的水平。对卵巢癌石蜡块的组织学切片进行免疫化学染色，检测因子VIII、CD34和VEGF。共研究了39例患者，不过并非所有患者都有配对的血清和腹水样本。对于每种血管生成因子，有以下发现：（a）血清和腹水中的浓度范围很广；（b）血清平均浓度高于正常血清平均浓度（P<0.05）；（c）血清平均浓度低于腹水平均浓度（P<0.05）。总体而言，血清和腹水浓度升高最一致的模式是bFGF。在血清样本中，38.9%的患者VEGF浓度正常，ANG为15.3%，bFGF为7.7%。在腹水中，24.5%的样本VEGF浓度在正常血清范围内，ANG为39.4%，bFGF为2.8%。在配对样本中，100%的样本VEGF和88.3%的样本bFGF腹水中浓度更高，而ANG为53.3%。一种因子的血清和/或腹水浓度与另一种因子的浓度之间无相关性，表明这些因子是独立调节的。抗CD34染色比抗因子VIII染色更敏感、可靠。VEGF染色在低分化肿瘤中最明显，且仅在肿瘤细胞上观察到。血管生成因子的血清或腹水浓度与肿瘤血管形成之间无相关性。晚期EOC与血清和腹水bFGF浓度升高有关，且在大多数情况下腹水中VEGF明显升高。血清VEGF以及血清和腹水ANG升高的情况较少见。血清和腹水中的血管生成谱与肿瘤血管形成之间无相关性。
