超声助力式弹性成像和剪切波弹性成像及超声造影特征与乳腺癌分子生物学指标的相关性

Correlations of ultrasound-assisted elasticity imaging, shear-wave elastography imaging and contrast-enhanced ultrasound features with molecular biological indexes of breast cancer

目的探讨二维超声、超声助力式弹性成像、剪切波弹性成像及超声造影的特征与乳腺癌分子生物学指标雌激素受体(estrogen receptor, ER)、孕激素受体(progesterone receptor, PR)、人表皮生长因子受体-2(human epidemic growth factor receptor-2, HER-2)、Ki-67之间的相关性。方法 160例疑诊乳腺癌患者,均行二维超声、助力式弹性成像、剪切波弹性成像和超声造影检查,观察超声声像特征,检测乳腺结节最大弹性模量值(maximum modulus of elasticity, Emax);绘制ROC曲线,评估Emax诊断乳腺良、恶性结节的效能;以组织病理结果为金标准,观察Emax诊断乳腺恶性结节的准确率;107例浸润性乳腺癌患者采用免疫组织化学法检测乳腺癌分子生物学指标ER、PR、HER-2、Ki-67阳性表达率,分析超声声像特征与ER、PR、HER-2、Ki-67阳性表达率的关系,采用Spearman相关性分析超声声像特征与ER、PR、HER-2、Ki-67的相关性。结果乳腺恶性结节110例,其中107例为浸润性乳腺癌;良性结节50例。剪切波弹性模量Emax最佳截断值为93.11 kPa时,诊断乳腺结节良、恶性的AUC为0.979(95%CI:0.960~0.990,P<0.001),灵敏度为93.64%,特异度为96.00%;以组织病理检查结果为金标准,Emax≥93.11 kPa诊断恶性乳腺结节的准确率为89.64%。浸润性乳腺癌患者形态不规则者ER阳性表达率(69.52%)高于形态规则者(20.00%)(P<0.05),结节直径<2 cm、形态不规则者PR阳性表达率(72.29%、67.82%)高于结节直径≥2 cm和形态规则者(30.51%、25.00%)(P<0.05),纵横比≥1、腋窝淋巴结转移者HER-2阳性表达率(73.86%、59.57%)高于纵横比<1、无腋窝淋巴结转移者(26.19%、20.00%)(P<0.05),弹性硬度评分>3分、Emax≥93.11 kPa、造影不均匀增强、造影范围增大>3 mm者Ki-67阳性表达率(91.76%、90.82%、91.58%、85.71%)高于弹性硬度评分≤3分、Emax<93.11 kPa、造影均匀增强、造影范围不变者(59.09%、44.44%、58.33%、60.87%)(P<0.05)。结节形态与ER阳性表达率呈负相关(r=—0.358,P<0.001),结节直径、形态与PR阳性表达率呈负相关(r=—0.732,P<0.001;r=—0.449,P<0.001),纵横比、腋窝淋巴结与HER-2阳性表达率呈正相关(r=0.493,P<0.001;r=0.342,P<0.001),弹性硬度评分、剪切波弹性成像、造影不均匀增强、造影范围增大与Ki-67阳性表达率呈正相关(r=0.725,P<0.001;r=0.566,P<0.001;r=0.642,P<0.001)。结论超声助力式弹性成像、剪切波弹性成像及超声造影的超声征象与ER、PR、HER-2、Ki-67阳性表达具有相关性,可无创性预测乳腺癌的侵袭性。

Objective To investigate the correlations of the characteristics of two-dimensional ultrasound, ultrasound-assisted elasticity imaging, shear-wave elastography images and contrast-enhanced ultrasound with the molecular biomarkers as estrogen receptor(ER), progesterone receptor(PR), human growth factor receptor-2(HER-2) and Ki-67 in patients with breast cancer. Methods Two-dimensional ultrasound, ultrasound-assisted elasticity imaging, shear-wave elastography and contrast-enhanced ultrasound were performed in 160 suspected breast cancer patients to observe the ultrasonographic features and detect the maximum modulus of elasticity(Emax) of breast masses. ROC curve was drawn to evaluate the efficacy of Emax on the diagnosis of benign and malignant breast tumors. The histopathological result was used as the gold standard to observe the accuracy of Emax on the diagnosis of malignant breast tumors. In 107 patients with invasive breast cancer, immunohistochemical method was used to detect the positive rates of ER, PR, HER-2 and Ki-67. The correlations of ultrasonographic features with the positive rates of ER, PR, HER-2 and Ki-67 were analyzed.Spearman correlation analysis was used to analyze the correlations of ultrasonographic features with ER,PR,HER-2 and Ki-67.Results In 110 patients with malignant breast tumors,there were 107 patients with invasive breast cancer.Benign breast tumors were confirmed in 50 patients.When the optimal cut-off value of shear-wave elastography imaging modulus Emax was 93.11 kPa,the AUCfor diagnosing benign and malignant breast tumors was 0.9786(95%CI:0.960-0.990,P<0.001),with a sensitivity of 93.64%,and specificity of 96.00%.The diagnosis accuracy of Emax≥93.11 kPa was 89.64%.The positive rate of ER was higher in patients with irregular shape of invasive breast cancer(69.52%)than that in patients with regular shape(20.00%)(P<0.05).The positive rates of PR were higher in patients with mass diameter<2 cm and irregular shape(72.29%,67.82%)than those in patients with mass diameter≥2 cm and regular shape(30.51%,25.00%)(P<0.05).The positive rates of HER-2 were higher in patients with aspect ratio≥1 and axillary lymph node metastasis(73.86%,59.57%)than those in patients with aspect ratio <1 and no axillary lymph node metastasis(26.19%,20.00%)(P<0.05).The Ki-67 positive rates were higher in patients with elastic hardness score>3,Emax ≥93.11 kPa,inhomogeneous enhancement,and contrast range >3 mm(91.76%,90.82%,91.58%,85.71%)than those in patients with elastic hardness score ≤3,Emax<93.11 kPa,homogeneous enhancement,and unchanged contrast range(59.09%,44.44%,58.33%,60.87%)(P<0.05).The tumor morphology was negatively correlated with the positive rate of ER(r=-0.358,P<0.001),the tumor diameter and morphology were negatively correlated with the positive rate of PR(r=-0.732,P<0.001;r=-0.449,P<0.001),the aspect ratio and axillary lymph nodes were positively correlated with the positive rate of HER-2(r=0.493,P<0.001;r=0.342,P<0.001),and elastic hardness score,shear-wave elastography images,inhomogeneous enhancement of contrast,and enlargement of contrast range were positively correlated with Ki-67 positive rate(r=0.725,P<0.001;r=0.566,P<0.001;r=0.642,P<0.001).Conclusion The ultrasonic signs of ultrasound-assisted elasticity imaging,shear-wave elastography imaging and contrast-enhanced ultrasound are correlated with the positive expressions of ER,PR,HER-2 and Ki-67,which could noninvasively predict the aggressiveness of breast cancer.