Correlation of the expression of vascular endothelial growth factor and its receptors with microvessel density in ovarian cancer

Abstract

The present study aimed to investigate the correlation between the expression of vascular endothelial growth factor (VEGF) and its receptors, the Flt-1 and KDR proteins, with clinical pathology and microvessel density (MVD) in ovarian cancer tissue. The protein expression levels of VEGF and its receptors, Flt-1 and KDR/Flk-1, were detected in 48 cases of ovarian cancer using the streptavidin-biotin complex (SABC) immunohistochemical method, and tumor MVD was evaluated using F8 factor (FVIII-RA). The expression of the VEGF, Flt-1 and KDR proteins was not significantly associated with the pathological type, extent of differentiation or clinical stage of ovarian cancer. However, the co-expression of VEGF and Flt-1 was markedly correlated with differentiation and clinical stage (P<0.01). The co-expression levels of VEGF and receptor Flt-1 in malignant neoplasms with lymph node metastasis was significantly higher compared with malignant neoplasms without lymph node metastasis (P<0.05). The expression level of KDR in patients with hepatic metastasis was significantly higher compared with patients without hepatic metastasis (P<0.05). The co-expression level of VEGF and KDR in patients with hepatic metastasis was significantly higher compared with patients without hepatic metastasis (P<0.05) and the Flt-1 expression level in patients with ascites <1,000 ml was significantly lower than that in patients with ascites ≥1000 ml (P<0.05). The mean MVD of VEGF- and KDR-positive patients was significantly higher compared with VEGF- and KDR-negative patients (P<0.05). The expression of VEGF and its receptors is involved in the malignant transformation of ovarian tumors, tumor progression and metastasis, as well as ascites formation and angiogenesis.

Keywords: Flt-1 receptor; KDR receptor; ascites; oophoroma; vascular endothelial growth factor.

Figure 1.

(A) Results of immunohistochemical staining for VEGF in ovarian cancer tissues. Microscopy showed that the tumor cell cytoplasm was stained, brown granules were visible and that consequently, VEGF expression was markedly positive. (B) Results of immunohistochemical staining for Flt-1 in ovarian cancer tissues. The tumor cells and stroma vessels were stained and the degree of vascular positive staining (arrows) was stronger. (C) Results of immunohistochemical staining for KDR in ovarian cancer tissues. Microscopy showed that brown granules were visible in the tumor cell cytoplasm, the nucleus was blue and that all the tumor cells were stained. VEGF, vascular endothelial growth factor. (A–C) Magnification, ×200.

Figure 2.

MVD of patients with positive VEGF/KDR expression (F8 was used as a vascular endothelial cell marker, SABC staining). Microscopy showed that the microvessels were abundant, and blood capillary clusters and slit-shaped vessels were visible (magnification, ×100). MVD, microvessel density; VEGF, vascular endothelial growth factor; SABC, streptavidin-biotin complex.