摘要
目的:研究乳腺浸润性导管癌的彩色像素密度(color pixel density,CPD)与血管内皮生长因子(vascular endothelial growth factor,VEGF)及多种临床预后预测指标—组织学分级、临床分期,肿块大小、淋巴结转移,雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor, PR)、C-erbB-2的相关性,旨在探讨多普勒超声定量指标—彩色像素密度(CPD)术前检测乳腺浸润性导管癌肿瘤血管生成情况及作为预后预测指标的临床应用价值。
材料与方法:52例乳腺浸润性导管癌的肿块。应用彩色多普勒超声(color doppler ultrasound,CDU)观察肿块血流信号的性质,并引出频谱多普勒(pulse doppler,PW),测定肿块的收缩期峰值血流速度(peak systolic velocity,PSV)和阻力指数(resistance index,RI)等血流动力学指标;运用能量多普勒超声(power doppler ultrasound,PDU)显示肿块内部及周边血流分布、形态情况并进行主观分级,同时选择血流最丰富的断面应用计算机软件计测肿块的彩色像素密度(CPD);对术后标本进行抗VEGF因子免疫组化染色,测量其阳性表达率,并对肿块的CPD值与VEGF进行相关性分析;术后收集肿块的相关资料(组织学分级、临床分期,肿块大小、淋巴结转移,ER、PR、C-erbB-2),并与CDP值进行相关性分析。
结果:(1)52例浸润性导管癌在不同组织学分级间血流分级差异具有统计学意义,且随组织学级别加大血流分级亦增高(H值=8.135、P=0.017);(2)52例肿块中40例频谱多普勒血流参数符合乳腺恶性肿瘤的PSV﹥20cm/s,RI≥0.7的血流特性,符合率为76.9%,且肿块内血流形态以中央穿入型和分支型为主,其中中央穿入型为最多见的肿瘤血管形态学特征,但二者在不同组织学分级间差异不具有统计学意义(P﹥0.05);(3)随着组织学分级、临床分期的加大,VEGF阳性率及CPD值增加、且组间差异具有统计学意义(P﹤0.01);(4)CPD值与VEGF具有较好的相关性(rs=0.851,P=0.000);(5) ER、PR、C-erbB-2阳性率在不同组织学分级、临床分期间差异无显著性(P﹥0.05),淋巴结转移的阳性率随组织学分级、临床分期的增高而增加(P﹤0.01);(6)CPD值与肿块大小、淋巴结转移、C-erbB-2具有良好相关性(rs=0.436 P=0.001),CPD值与ER、PR无相关性(P﹥0.05)。
结论:多普勒超声对乳腺浸润性导管癌肿块的血流形态学及动力学指标的检测可为其诊断、鉴别诊断提供更多有价值的信息,但作为临床独立预后预测指标价值有限;应用能量多普勒超声显示肿瘤血管情况并定量计测肿块CPD值与术后免疫组化法检测的VEGF阳性率具有良好相关性,这说明彩色像素密度作为临床预后预测指标具有可行性和一定程度的可靠性;CPD值与肿块大小、组织学分级、淋巴结转移情况、临床分期、C-erbB-2具有良好相关性,这说明其作为临床独立预后预测指标具有一定的可靠性和可信度。
Objective: To discuss clinical application value about quantified indicator CPD of doppler ultrasound evaluating tumor angiogenesis and preoperative prognosis,by studying the correlation between color pixel density and vascular endothelial growth factor、some clinical prognostic indicator (histology grading、TNM stage、tumor size、lymph node metastasis、ER、PR、C-erbB-2) of breast invasive ductal carcinoma.
Materials and methods:52 patients with breast invasive ductal carcinoma were performed by doppler ultrasound. The features of blood flow in neoplasm were evaluated by color doppler ultrasonography, the most prominent internal and peripheral vessels of the neoplasm were examined with pulse wave doppler to judge the quality of the signal, measure the peak systolic velocity、resistive index .The number, shape and distribution of the internal and peripheral vessels of the neoplasm were tested, and the area with the richest blood flow was chosen to calculate color pixel density with computer-assistant of power doppler ultrasonography .The vascular endothelial growth factor was measured in surgical specimen after immunohistochemical staining using anti-factor VEGF and evaluated the correlation between color pixel density and VEGF、some clinical prognostic indicator (histology grading、TNM stage、tumor size、lymph nodes metastasis、ER、PR、C-erbB-2) of breast invasive ductal carcinoma. Results:(1)The grade of blood stream signal is increasing following histology grading growing, and the blood stream signal has statistical significant in the different histology grading(H=8.135、P=0.017). (2)The peak systolic velocity and resistive index of vascular structures be calculated by pulse wave doppler ,there are 40 tumors of PV﹥20cm/s、RI≥0.7,showing rate 76.9%,and center,penetrating vascular structure is most significance, especially center , but these index have no statistical significant(P﹥0.05).(3)The higher of histology grading and TNM stage ,the greater of VEGF-positive and CPD, and has statistical significant in the different histology grading and TNM stage(P﹤0.01).(4) Color pixel density as quantified indicator of color power doppler showed a good correlation with the vascular endothelial growth factor(rs=0.851,P=0.000).(5) ER、PR、C-erbB-2 positive rate has no statistical significant in the different histology grading and TNM stage, but lymph nodes is opposite;(6) Color pixel density is correlated significantly with tumor size、lymph nodes metastasis、C-erbB-2,but there is not the correlation with ER、PR.
Conclution: By utilizing color Doppler ultrasound for analyzing the blood stream shaping and dynamics of the patients with breast invasive ductal carcinoma can provide more information in diagnosis and differential diagnosis ,but clinical prognostic evaluation is helpless; Color pixel density as quantified indicator showed a good correlation with the vascular endothelial growth factor, which means to color pixel density be able to assess clinical prognostic; Color pixel density is a reliable clinical prognostic indicator ,because of a good correlation with tumor size、histology grading、lymph nodes metastasis、C-erbB-2.
引文
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