Endothelial cell activation and proliferation in ovarian tumors: two distinct steps as potential markers for antiangiogenic therapy response.

Ovarian cancer is the second leading cause of cancer-related death in women worldwide. Since most patients are diagnosed in advanced disease stages, the starting point, early steps and molecular mechanisms of ovarian cancer angiogenesis are still incompletely characterized. Most immunohistochemical studies for assessment of microvessel density (MVD) in ovarian tumors are based on CD31, CD34 and CD105 immunostaining of tumor blood vessels. Yet, the proliferative status of tumor blood vessel endothelial cells has not as yet been used in the assessment of tumor blood vessels. The present study investigated the Ki67 proliferative index of tumor blood vessel endothelial cells highlighted with the CD34 panendothelial marker and the CD105 endothelial marker in ovarian cancers by antigen co-localization with a doublestaining immunohistochemical method. Lack of co-localization of CD105 and Ki67 in all types of ovarian tumors together with the presence of CD34+/Ki67-positive endothelial cells suggest that endothelial cell activation and proliferation are distinct steps in ovarian tumors. Differences in the proliferation index were observed in endothelial cells from blood vessels of the tumor core and those of the tumor peripheral zones. Potential specific targeting of activated and proliferating tumor blood vessels may provide clues for improving antiangiogenic therapy efficiency.