Neuropilin-1 and VEGF correlate with somatostatin expression and microvessel density in ovarian tumours.

Vascular endothelial growth factor (VEGF), is an angiogenic growth factor, expressed more highly in malignant than benign ovarian tumours. Neuropilin-1, which can act as a VEGF receptor has been shown to be associated with tumour angiogenesis in some cancer systems. Somatostatin (SST), a potentially anti-angiogenic factor, acts via somatostatin receptors that are expressed in ovarian cancer. We used immunohistochemistry to demonstrate expression of Neuropilin-1 in 63 malignant and 35 benign ovarian tumours and compared it to VEGF, Flt, Flk, SST expression and tumour microvessel density (MVD). Neuropilin-1 was expressed in 34/63 malignant and 22/35 benign lesions. VEGF, Flt, Flk and SST were expressed more highly in the epithelium of malignant and the vessels of benign lesions. VEGF expression correlated with SST expression in the epithelium (p<0.001) and the vessels (p<0.001), this co-expression was confirmed by dual immunostaining. The MVD for malignant lesions was higher than benign (p<0.001) and positively correlated to epithelial VEGF expression (p=0.001) and negatively correlated to vascular VEGF expression (p=0.025). These results show that Neuropilin-1 is expressed in ovarian tumours and also show that VEGF and SST are co-expressed in the same tissue compartments raising the intriguing possibility that SST may be important in angiogenesis in ovarian cancer.

Use of dynamic contrast-enhanced MRI to assess the functional vascular pharmacokinetic parameters of normal human ovaries.

OBJECTIVE: To assess the ability of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to measure functional vascular pharmacokinetic parameters of normal human ovaries in vivo using an open linear two-compartment pharmacokinetic model. STUDY DESIGN: Twenty-one women with no ovarian disease underwent DCE-MRI. Sequential images were acquired during injection of a contrast bolus. Ovarian volumes were calculated and pharmacokinetic data analyzed using a pharmacokinetic model. Ovarian tissue was compared with skeletal muscle to demonstrate the pharmacokinetic parameters. RESULTS: Normal ovarian tissue was found to enhance rapidly and dramatically. When compared with skeletal muscle as a control, ovarian tissue was seen to demonstrate a significantly higher maximum enhancement factor and amplitude of the upslope, although there was no significant difference in the exchange rate. Sample size precluded conclusions about differences due to menstrual cycle or menopausal status. CONCLUSION: The results reflect the vascular physiology of the normal ovary. Definition of the pharmacokinetic properties of normal ovaries will allow DCE-MRI to be applied prospectively to conduct noninvasive, in vivo studies of ovarian angiogenic function, including response to drugs, contraceptive research, assessment of polycystic ovary syndrome, ovarian hyperstimulation syndrome, diagnosis of malignancy and prediction of response to antiangiogenic chemotherapy.