Correlation of real-time gray scale contrast-enhanced ultrasonography with microvessel density and vascular endothelial growth factor expression for assessment of angiogenesis in breast lesions

Objective. The purpose of this study was to determine the correlation of real-time gray scale contrast-enhanced ultrasonographic (CEUS) patterns and parameters with microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression for assessment of angiogenesis in breast lesions. Methods. Real-time gray scale CEUS was performed in 53 women with breast lesions. Contrast-enhanced ultrasonographic patterns and quantitative parameters were analyzed. Mean MVD and VEGF expression in breast lesions were measured by immuno-histochemical analysis. Results. Surgical pathologic analysis showed 25 benign and 28 malignant lesions. Different CEUS patterns were observed in the high- and low-MVD and -VEGF groups. Microvessel density and VEGF expression were significantly associated with heterogeneous enhancement with or without perfusion defects and radial or penetrating vessels surrounding the lesions (P <.05). The enhancement order and degree were significantly related to MVD (P <.01) but not correlated with VEGF expression (P >.05). Malignant and benign lesions did not differ significantly in time-intensity parameters (P >.05). The peak intensity, rise in intensity, maximum rise slope of the curve, wash-out slope of the curve, and area under the time-intensity curve (area) were statistically correlated with MVD (P <.05). The highest correlation (r=0.56; P <.001), however, was between the area and MVD. No significant association was found between any CEUS parameters and VEGF expression (P >.05). Conclusions. Contrast-enhanced ultrasonographic patterns and parameters of breast lesions are more closely correlated with MVD than VEGF expression. Real-time gray scale CEUS has a potential role in evaluating angiogenesis in breast lesions, but CEUS parameters are not correlated with the malignancy or benignity of breast tumors.