| Objective: 1) To investigate the characteristics of contrast-enhanced ultrasonography in breast cancer marginal zone, and to screen the qualitative and quantitative parameters of contrast-enhanced ultrasound with good correlation of prognostic factors of breast cancer. 2) To study the distribution characteristics of malignant matrix in the marginal zone of breast cancer, and to clarify the relationship between the difference of regional distribution of malignant matrix and qualitative and quantitative parameters of ultrasonic contrast in breast cancer. 3) To investigate the characteristics of tumor vascular heterogeneity in the marginal zone of breast cancer, and to clarify the relationship between differences of tumor vessels and vascular mimicry regional distribution and qualitative and quantitative parameters of ultrasonic contrast in breast cancer. Methods: 1) To get conventional ultrasound to select the best view of the suspected breast cancer by the flow distribution, and to observe the qualitative indexes and the perfusion parameters of the central area, marginal zone and the breast tissue adjacent to the lesion. To mark research section and marginal zone that need to be drawn by methylene. 2) 119 cases of breast cancer were included in the study. The clinical pathological parameters and molecular biological parameters were collected to analyze the correlation between the ultrasonic contrast characteristics and the prognostic factors in breast cancer. To screen out qualitative and quantitative parameters of contrast-enhanced ultrasound which have a good correlation with the prognosis factors of breast cancer. To screen out tumor microcirculation related prognosis factors associated with contrast-enhanced ultrasound. 3) After the surgery, breast cancer was sampled in the three regions including the edge, the central area and the para carcinoma tissuer in the study section to carry out the immunohistochemical detection. To analysis relevance between distribution differences of malignant stromal cells TAM, TADC and TAF and the parameters of contrast-enhanced ultrasound in three different regions of breast cancer. 4) To utilize immunohistochemical staining for CD34 to mark tumor microvessel, and to use CD34/PAS double staining to mark tumor vascular mimicry. To study the correlation between regional distribution difference on MVD of breast cancer and vascular mimicry and ultrasonic contrast parameters. Results: 1) The difference of the time intensity curve of the three regions of the breast cancer was statistically significant. The median intensity, peak intensity, rise time, mean transit time, and the area under the time intensity curve of the breast cancer marginal zone were higher than those in the central area of the tumor and the adjacent breast tissues(P<0.05). The tumor size, histological grade and clinical stage of the 3 prognostic factors associated with the most of the contrast-enhanced ultrasound qualitative indicators. In the qualitative indexs of contrast-enhanced ultrasound, the indexes of the perfusion defect, enhancement degree and the range of lesion enhancement were correlated with the most of the prognostic factors. Among them, the correlation between perfusion defects and prognosis was the strongest. Median intensity, rising slope, initial intensity, descending slope and time to peak were closely related to prognosis factors. Quantitative parameters of contrast-enhanced ultrasound in the margin of breast cancer associated with added and more concentrated prognostic factors than qualitative indexs. Almost all intensity parameters and perfusion slope parameters of contrast-enhanced ultrasound of breast cancer marginal zone were correlated with contrast mode and degree of contrast in qualitative indexs. 2) The infiltration quantity of TAF and TAM were decreasing in three regions of the marginal zone, the central area and the adjacent region of the tumor(P<0.05), while that of TADC showed increasing distribution(P<0.05). The relationship between malignant stromal tumor and breast cancer showed that the distribution of TAM and TAF was not strong correlated with the enhanced range of contrast-enhanced ultrasonography in the three breast cancer regions(P>0.05), however, the phenomenon was found that the immature DC accumulate in the central area of the tumor when enhanced range of ultrasound was larger than that of the two-dimensional ultrasound after contrast(P<0.05). TAF and TADC were low expression in the central region of the breast cancer with filling defect, TAM was high expression in the marginal zone and the central area, and the enhancement degree was closely related to TAM and TADC and TAF in the three regions, which showed that TAM and TAF are highly expressed in the marginal zone and the central region of high enhance. TADC were all low expression in the three regions. The relationship between malignant matrix and related prognostic factors of tumor microcirculation showed that TAF and TAM had positive corion with tumor size in the marginal zone, but there was negative correlation between TADC and tumor size in the central region. And malignant matrix are associated with clinical stage and histological grade in breast cancer each region. 3) The distribution of MVD and vascular mimicry were degressive in the breast cancer marginal zone, the central area and the adjacent breast tissue(P<0.05). The correlation between MVD and contrast-enhanced ultrasound was not consistent with the correlation between VM and contrast-enhanced ultrasound. The quantitative parameters of contrast-enhanced ultrasound in the central area and cancer edge of the cancer were associated with MVD. The filling defect in the qualitative index of the contrast-enhanced ultrasound was associated with the MVD in the central area of the breast cancer. The degree of enhancement was associated with MVD in three regional in breast cancer. The range of lesion enhancement was not associated with MVD. There was no association between the quantitative parameters of contrast-enhanced ultrasound and the positive rate of VM in the three regions. The positive rate of VM in breast cancer edge with filling defect was higher but lower in central area. The enhancement degree and the enhancement range were not associated with the positive rate of VM in each region. The correlation between MVD and tumor microcirculation related prognostic factors was not consistent with the correlation between VM and tumor microcirculation related prognostic factors. When the histological grade increased, the MVD in the marginal zone and the central area of the breast cancer was also higher. However, the size of the lesion and clinical stage were not associated with MVD in the three regions of the breast cancer. The positive rate of VM was higher when the clinical stage was higher and the lesion was larger. When the histological grade was higher, the positive rate of VM was higher in the three regions. Conclusion: 1) The qualitative indexes of contrast-enhanced ultrasound for the prognosis of breast cancer were filling defect, enhancement degree and lesion enhancement range. The quantitative parameters of contrast-enhanced ultrasound for the prognosis of breast cancer were median intensity, rising slope, initial intensity, descending slope and time to peak. The tumor size, histological grade and clinical stage of the 3 prognostic factors were tumor microcirculation related prognostic factors of breast cancer. There was no significant correlation between the main differential diagnosis indexs and the prognosis factors. 2) The correlation was not consistent between the parameters of contrast-enhanced ultrasound and the malignant matrix in the breast cancer marginal zone and the central area. The correlation between the contrast-enhanced ultrasound indexs and the malignant stroma of the margin was stronger than that of the central area. TAM and TAF tend to be concentrated in the area with dense microvessels, but TADC was inhibited by breast cancer tumor microvessels. The relationship between malignant stromal and tumor microcirculation related prognostic factors showed that malignant stromal cells in three different regions were associated with clinical stage and histological grade, but the association between malignant stromal tumor size and tumor size was not balanced. The TAF and TAM of the marginal zone of the breast cancer are related to the bad prognosis. The TADC of three regions were protective factors for breast cancer. 3) The correlation between MVD and contrast-enhanced ultrasound was not consistent with the correlation between VM and contrast-enhanced ultrasound. Contrast-enhanced ultrasound can not completely reflect MVD, but it can truly reflect the function of tumor blood vessels. VM had important value in reflecting the invasion of tumor margins. The breast cancer tissues near the liquefaction necrosis area may have a microcirculation construction of higher malignancy degree and more malignant biological behavior. The correlation between contrast-enhanced ultrasound and MVD was significantly better than the correlation between contrast-enhanced ultrasound and VM, but was associated with prognostic indicators more than MVD. It showed that VM was closely related to the differentiation degree and invasion force of breast cancer cells. The combination of contrast-enhanced ultrasound and VM can not only reflect the growth of tumor, but also predict the growth vessel, metastasis and recurrence of tumor. |
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