Correlation Between Angiogenesis Assessed By 3D-power Doppler Ultrasound And MVD In Early Stage Cervical Carcinoma

PrefaceMalignant tumors are highly dependent on vascularization for their growth and spread. Three-dimensional (3D) power Doppler ultrasound is a non-invasive technology that evaluates the blood flow of pelvic organs. Three-dimensional power Doppler ultrasound is a relatively new technique that allows tumor vascularization assessment, both quantitatively by means of 3D-PDU-derived vascular indices and qualitatively by depicting three-dimensionally the tumor vascular network. Some studies have shown that Doppler assessment of tumor vascularization is related to microvessel density in ovary and breast cancer.The aim of the present study was to evaluate whether differences exist in vascularization as assessed by 3D-PDU in early stage cervical carcinoma and in cervical intraepithelial neoplasm (CIN) and in normal controls; and to find the correlation between tumor angiogenesis assessed by 3D-power Doppler ultrasound and MVD in early stage cervical carcinoma.Materials and MethodsFrom November 2005 to October 2006, an analysis was performed of 27 women with cervical carcinoma and 14 women with CIN at Second Hospital, China Medical University. During the study period, 15 women with normal uterine cervix agreed to undergo 3D power Doppler examinations and were selected as controls. All the patients underwent 3D power Doppler examination during one to three days prior to surgery. All the cervical carcinoma patients were staged clinically according to the staging system of the International Federation of Gynecology and Obstetrics (FIGO).The equipment used in the study was GE VOLUSON 730 Expert with 5-9 MHz trans vaginal transducers.Each patient underwent systematic gray-scale examination of uterus and ovaries with special emphasis on the cervix. Following B-mode evaluation, the two-dimensional power Doppler gate was activated to assess vascularization. Resistance Index (RI) and Peak Systolic Velocity (PSV, cm/s) were recorded automatically. And then the three-dimensional power Doppler mode was switched on. The Virtual Organ Computer-aided Analysis (VOCAL) program then automatically calculated gray-scale and color values. According to these values the indices were calculated: Vascularization Index (VI), Flow Index (FT), Vascularization Flow Index (VFI).All clinicopathologic data were obtained. All the cervical tissue samples were obtained after operation. MVD of the tissue samples was assessed by immunohistochemical method (SP method).All statistical analysis were performed using the SPSS 11.5 statistical package which involves Kolmogorov-Smirnov test, Kruskal-Wallis test, Mann-Whitney test and Spearman correlation analysis. A P-value < 0.05 was considered to be statistically significant.Results1. There was a significant positive correlation between MVD and VI, VFI(r=0.776, r=0.717).2.Significant differences between means for normal controls and cervical carcinoma were found for following parameters: RI, VI, VFI, MVD. And significant differences between means for normal controls and CIN were found for the same parameters. The VI, VFI, MVD in cervical carcinoma were significantly higher than that in normal tissues and CIN, the RI in cervical carcinoma was significantly lower than that in normal tissues and CIN. Significantly higher VI and MVD values were noted in cervical carcinoma compared with CIN.3.The relationship of clinicopathological characteristics and 3D-PDU parameters or MVD in early stage cervical carcinoma:(1) Significantly higher VI and MVD values were noted in Stage II tumors compared with Stage I tumors.(2) There were no significant differences in all values regard to histologic grades.(3) Significant differences between means for tumors with pelvic lymph node metastases and tumors without pelvic lymph node metastases were found for following parameters: VI, VFI, MVD and RI. ROC curve showed cut off values were 8.0%, 4.25, 32.5, 0.46, respectively. The positive likelihood ratio (LR_+) of these cut off values were 2.9, 2.18, 3.64, 1.94, respectively.Conclusions1 .VI, VFI were significant correlated with MVD. Thus, VI and VFI could be used as useful in vivo indicators of tumor angiogenesis in cervical carcinoma.2.The quantified indices using 3D power Doppler helped to differentiate cervical carcinoma from CIN and normal cervix.3.The quantified indices using 3D power Doppler, corresponding with the stage in cervical carcinoma, helped to judge the stage of the tumors.4.The quantified indices using 3D power Doppler showed more worthful than RI and PSV in predicting pelvic lymph node metastasis. VI, VFI could be used as new parameters for predicting pelvic lymph node metastasis potential before operation in cervical carcinoma.