Correlation of Contrast-enhanced Ultrasound with Expression of Hypoxia Inducible Factor-1α in Transplanted Mice Mammary Cancer

Abstract

To investigate the correlation of contrast-enhanced pattern with expression of hypoxia inducible factor-1α (HIF-1α) and microvessel density (MVD) in mice breast cancer. A total of 22 mice were implanted with breast cancer cells (Ca761) subcutanously in the thigh. The tumors were examined with conventional ultrasound and contrast-enhanced ultrasound (CEUS) on days 4,6,7,8,9,10,and 11 after implantation and then sacrificed. Three or four mice were included each time. Expressions of HIF-1α and MVD in cancer tissues were detected immunohistochemically. Correlation of contrast-enhanced patterns with expression of HIF-1α and MVD in breast cancer was analyzed. Mice were divided into 3 groups according to the tumor volume:group 1 (volume<0.05 cm(3),n=5),group 2 (volume 0.05-0.75 cm(3),n=9),and group 3 (volume>0.75 cm(3),n=8). The CEUS pattern was different in different groups:four mice in group 1 presented as type 1 (peripheral ring enhancement with no enhancement within the tumor) and 1 case presented as type 2 (peripheral ring enhancement with deep penetration). Most mice in group 2 presented as type 3 (homogeneous or heterogeneous enhancement in the whole tumor,n=5). In group 3,most mice presented as type 4 (peripheral ring enhancement with focal nodular enhancement within the tumor,n=7). Contrast-enhanced pattern was significantly different in different volume groups (P<0.01). Enhanced pattern (type 1-4) was closely correlated with tumor volume (r=0.841,P<0.05). The expression of HIF-1α was negatively correlated with enhanced patterns (type 1-4) (r=-0.596,P＝0.003),but not with tumor volume (P>0.05). There was no significant difference in MVD values between different enhanced patterns (type 1-4),and there was no correlation between the MVD and tumor volumes (P>0.05). CEUS can be used as a noninvasive tool to monitor tumor angiogenesis in tumor and the enhanced patterns may reflect the expression of HIF-1α inside the tumor.