Expression Of Vascular Endothelial Growth Factor Receptors: Flt-1,KDR In Cerebral Arteriovenous Malformations

Objectives: The precise mechanisms responsible for the genesis, development and rupture of the cerebral arteriovenous malformation (cAVM) remain unclear. Many investigations showed the high expression of gowth factors in cerebral vascular disease. And the close relationship between VEGF (Vascular Endothelial Growth Factor) and cAVM has attracted attention recently. In this report, we examined the expression of VEGF receptors: Flt-1, KDR in cAVM and contrasted with that in normal brain vasculars. We also investigated the potential effect of Flt-1, KDR on the genesis, development of cAVM and the possible relationship between the expression of Flt-1, KDR and clinical features of cAVM.Methods: The specimens consisted of 42 cAVM tissues obtained from patients who underwent surgery in the department of neurosurgery in Huaxi Hospital from June 2005 to August 2006. 16 normal brain vasculars were used as control, which obtained from cranial brian trauma patients who underwent lobectomy during the same period. We observed the construction features of the vascular wall involved in the cAVM nidus and examined the expression of Flt-l, KDR in cAVM specimens via immunohistochemical techniques. Results: Positive staining of Flt-1,KDR was observed chiefly in the endothelial cells and smooth muscle cells of the vascular wall involved in the cAVM nidus.The positive rate was 66.67% (28/42) for Flt-1 and 57.14% (24/42) for KDR respectively. Which was significantly higher than that of normal brain vasculars ( Z = -2.377,p=0.017＜0.05 and Z =-2.619,p=0.009＜0.05). The positive rate of Flt-1 was significantly higher in large group (x~2 = 4.773, p = 0.029＜0.05 ), but without significant differences for the positive rate of KDR (p＞0.05). The expression of Flt-1, KDR in cAVM had no significant relationship with patient's age, Spetzler gradation and whether cAVM rupture or not.Conclusions:1. The expression of Flt-1, KDR in cAVM nidus is significantly higher than that of normal brain vasculars, which indicates that Flt-1, KDR may play an effective role in the development of cAVM.2. The positive rate of Flt-1 was significantly higher in large group, but without significant differences for the positive rate of KDR. The expression of Flt-1, KDR in cAVM had no significant relationship with patient's age. So Flt-1, KDR can't be considered as the only responsible factor for the development of cAVM.3. As there is no correlation between Flt-1, KDR expression and Spetzler gradation and whether cAVM rupture or not, Flt-1 and KDR can't be used as the index of cAVM rupture.