Detection of tumor-associated neoangiogenesis by Doppler ultrasonography during early-stage ovarian cancer in laying hens: a preclinical model of human spontaneous ovarian cancer.

Objective: Tumor-associated neoangiogenesis (TAN) is one of the earliest events in ovarian tumor growth and represents a potential target for early detection of ovarian cancer (OVCA). Because it is difficult to identify patients with early-stage OVCA, the goal of this study was to explore a spontaneous animal model of in vivo ovarian TAN associated with early-stage OVCA detectable by Doppler ultrasonography (DUS).

Methods: White Leghorn laying hens were scanned transvaginally at 15-week intervals up to 45 weeks. Gray scale ovarian morphologic characteristics and Doppler indices were recorded. Hens were euthanized at diagnosis for ultrasonographic morphologic/vascular abnormalities or at the end of the study (those that remained normal). Ovarian morphologic and histologic characteristics were evaluated. Vascular endothelial growth factor (VEGF) and alpha(v)beta(3)-integrin expression was assessed by immunohistochemical analysis. Doppler ultrasonographic observations were compared with histologic and immunohisto-chemical findings to determine the ability of DUS to detect ovarian TAN.

Results: Significant changes in ovarian blood flow parameters were observed during transformation from normal to tumor development in the ovary (P < .05). Tumor-related changes in ovarian vascularity were identified by DUS before the tumor became detectable by gray scale imaging. Increased expression of VEGF and alpha(v)beta(3)-integrins was associated with tumor development. Ovarian TAN preceded tumor progression in hens.

Conclusions: The results suggest that ovarian TAN may be an effective target for the detection of early-stage OVCA. The laying hen may also be useful for studying the detection and inhibition of ovarian TAN using various means, including the efficacy of contrast agents, targeted molecular imaging, and antiangiogenic therapies.