Proangiogenetic molecules, hypoxia-inducible factor-1alpha and nitric oxide synthase isoforms in ovarian endometriotic cysts.

Endometriosis is a common disease characterised by ectopic growth of endometrial tissue outside the uterine cavity. Angiogenesis has been implicated in the pathogenesis of the disease; some molecules, like hypoxia-inducible factor-1alpha (HIF-1alpha) and neuronal, endothelial and inducible nitric oxide synthase isoforms (nNOS, eNOS and iNOS), are known as proangiogenetic factors. We evaluated expression of these molecules by immunohistochemistry in 32 cases of ovarian endometriomas, formalin-fixed and paraffin-embedded. Analysis was focused on the cells composing the inner layer of the cyst, constituted by the ectopic endometrial glands, stromal cells and vessels, and the outer one, constituted by a fibrous layer of fibroblasts and vessels. We found that epithelial glands and capsular vessel endothelial cells showed a correlated expression of NOS isoforms; that expression of nNOS, iNOS and HIF-1alpha was correlated in epithelial glands and capsular fibroblasts; that vessel endothelial cells showed a higher mean expression for all the proangiogenetic molecules in the outer layer than in the inner one; and that capsular fibroblasts showed a higher mean expression for HIF-1alpha, iNOS and eNOS compared to the specialised stromal cells of the inner layer. Our data seem to indicate that angiogenesis is stimulated more in the outer capsule than in the inner layer of ovarian endometriotic cysts. The knowledge of the complex mechanisms associated to angiogenesis might be useful in a therapeutic approach of ovarian endometriosis based on anti-angiogenetic drugs. The therapeutic target would be mainly the capsular vasculature, more than the vasculature of ectopic endometrial tissues.