Abu-Jawdeh G M, Faix J D, Niloff J, Tognazzi K, Manseau E, Dvorak H F, Brown L F
Department of Pathology, Beth Israel Hospital, Boston, Massachusetts 02115, USA.
Lab Invest. 1996 Jun;74(6):1105-15.
Angiogenesis is a critical factor in the growth, progression, and metastatic spread of solid tumors. Furthermore, angiogenesis has been correlated with prognosis in patients with ovarian cancer. The pathogenesis of the angiogenic events in ovarian cancer, however, are not well defined. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is a multifunctional cytokine that has been shown to be an important regulator of tumor angiogenesis. The purpose of the present study was to define the expression of VPF/VEGF and its receptors flt-1 and KDR in ovarian tumors. Four specimens of normal ovarian cortex and 41 specimens of benign (4), borderline (8), and malignant (29) ovarian tumors were studied by in situ hybridization, and in some cases by immunohistochemical analysis. VPF/VEGF protein was also determined by an immunofluorometric assay in cyst fluids obtained from 11 patients, including 7 benign, 2 borderline, and 2 malignant tumors. VPF/VEGF mRNA and protein were expressed by the neoplastic cells in all of the malignant tumors evaluated, with the majority of tumors (28 of 29) showing strong expression of mRNA. Serous borderline tumors had variable VPF/VEGF mRNA expression, with two of six cases showing focal strong expression and four showing low-level expression. No definite expression of VPF/VEGF was seen in two cases of mucinous borderline tumors. No strong expression of VPF/VEGF mRNA was observed in normal ovarian cortex, including surface epithelium, or benign tumors. Substantially higher VPF protein concentrations were detected in cyst fluids of the two malignant (60, 440 pM) and two borderline tumors (210, 590 pM) than in the seven benign serous cysts (mean, 10 +/- 3 pM). In addition, microvascular endothelial cells strongly expressed mRNA of the VPF/VEGF receptors flt-1 and KDR and immunostained for VPF/VEGF protein in the majority of malignant and borderline tumors examined. These findings suggest that VPF/VEGF plays an important role in the angiogenesis associated with ovarian neoplasms.
血管生成是实体瘤生长、进展和转移扩散的关键因素。此外，血管生成与卵巢癌患者的预后相关。然而，卵巢癌中血管生成事件的发病机制尚未明确。血管通透因子/血管内皮生长因子（VPF/VEGF）是一种多功能细胞因子，已被证明是肿瘤血管生成的重要调节因子。本研究的目的是确定VPF/VEGF及其受体flt-1和KDR在卵巢肿瘤中的表达情况。通过原位杂交，在某些情况下还通过免疫组织化学分析，对4例正常卵巢皮质标本和41例良性（4例）、交界性（8例）及恶性（29例）卵巢肿瘤标本进行了研究。还通过免疫荧光分析法测定了11例患者囊肿液中的VPF/VEGF蛋白，其中包括7例良性、2例交界性和2例恶性肿瘤。在所有评估的恶性肿瘤中，肿瘤细胞均表达VPF/VEGF mRNA和蛋白，大多数肿瘤（29例中的28例）显示mRNA强表达。浆液性交界性肿瘤的VPF/VEGF mRNA表达各异，6例中有2例显示局灶性强表达，4例显示低水平表达。2例黏液性交界性肿瘤未观察到VPF/VEGF的明确表达。在正常卵巢皮质（包括表面上皮）或良性肿瘤中未观察到VPF/VEGF mRNA的强表达。与7例良性浆液性囊肿（平均10±3 pM）相比，2例恶性（60、440 pM）和2例交界性肿瘤囊肿液中的VPF蛋白浓度显著更高。此外，在大多数检查的恶性和交界性肿瘤中，微血管内皮细胞强烈表达VPF/VEGF受体flt-1和KDR的mRNA，并对VPF/VEGF蛋白进行免疫染色。这些发现表明VPF/VEGF在与卵巢肿瘤相关的血管生成中起重要作用。
