二维超声特征联合超声弹性应变率比值在乳腺癌中的诊断价值及与病理预后指标的相关性分析.pdf

二维超声特征联合超声弹性应变率比值在乳腺癌中的诊断价值及与病理预后指标的相关性分析吴静，李景成都医学院第二附属医院（核工业四一六医院）超声医学科，四川 成都 610051【摘要】目的：分析二维超声特征联合超声弹性应变率比值（SR）在乳腺癌中的诊断价值及与病理预后指标的相关性。方法：选取2020年1月2021年12月成都医学院第二附属医院收治的265例乳腺肿瘤患者临床资料。经病理检查确诊：良性病变171例（良性组），恶性病变94例（恶性组）。收集二维超声及超声弹性成像检查图像资料，对比两组二维超声表现特征、SR值，并统计雌激素受体（ER）、孕激素受体（PR）、原癌基因（CerbB-2）阳性率。绘制受试者工作特征（ROC）曲线，计算二维超声、SR值对乳腺癌诊断效能，以Pearman相关性分析二维超声征象、SR值与ER、PR、CerbB-2相关性。结果：恶性组二维超声特征中有毛刺征、后方回声衰减、微钙化、淋巴结转移、血流丰富者及SR值明显高于良性组（P0.05）。恶性组ER、PR、CerbB-2阳性率分别为59.57%、75.53%、47.87%，明显高于良性组（P0.05）。绘制ROC曲线显示，二维超声、SR值对乳腺癌诊断价值 AUC值分别为 0.586、0.743，联合诊断 AUC值为 0.761，联合检测效果明显高于两者单独检测（P0.05）。ER阳性者有毛刺征、后方回声衰减、SR值高于ER阴性者（P0.05）；PR阳性者有淋巴结转移、SR值高于PR阴性者（P0.05）；CerbB-2阳性者有微钙化、SR值高于CerbB-2阴性者（P0.05）。经Pearman相关性分析，二维超声征象毛刺征、后方回声衰减与ER正相关，淋巴结转移与PR正相关，微钙化与CerbB-2正相关，SR值与ER、PR、CerbB-2正相关（P0.05）。结论：二维超声特征联合超声SR值可为乳腺癌诊断提供可靠影像学信息，毛刺征、后方声衰减、淋巴结转移、微钙化征象及SR值与患者病理预后指标ER、PR、CerbB-2之间存在一定关系。【关键词】乳腺癌；二维超声；超声弹性应变率比值；病理【中图分类号】R737.9【文献标志码】A【文章编号】1005-202X（2024）02-0175-06Diagnostic value of breast cancer with 2D ultrasound features combined with ultrasonic elasticstrain rate ratio and correlation analysis with pathological prognostic indicatorsWU Jing,LI JingDepartment of Ultrasound Medicine,The Second Affiliated Hospital of Chengdu Medical College(China National Nuclear Corporation416 Hospital),Chengdu 610051,ChinaAbstract:Objective To analyze the diagnostic value of two-dimensional(2D)ultrasound features combined with ultrasonicelastic strain rate ratio(SR)for breast cancer and discuss their correlations with pathological prognostic indicators.MethodsThe clinical data of 265 patients with breast cancer admitted to the 2nd Affiliated Hospital of Chengdu Medical College fromJanuary 2020 to December 2021 were analyzed retrospectively.Through pathological examination,171 cases were diagnosedwith benign lesions(benign group)and 94 cases with malignant lesions(malignant group).The 2D ultrasound and ultrasoundelastography imaging data were collected and compared for the two groups in terms of ultrasound appearance and SR.Thepositive rates of estrogen receptor(ER),progesterone receptor(PR),and proto-oncogene(CerbB-2)were recorded.Receiveroperating characteristic(ROC)curve was drawn to analyze the diagnostic efficiency of 2D ultrasound and SR for breastcancer;and Pearman correlation analysis was conducted to assess the correlations between 2D ultrasound features/SR andER/PR/CerbB-2.Results The 2D ultrasound features such as spicule sign,posterior echo attenuation,microcalcification,lymph node metastasis,and abundant blood flow were more common in malignant group,and the SR was significantly higherthan that in benign group(P0.05）。本研究经成都医学院第二附属医院（核工业四一六医院）超声医学科伦理委员会审查通过（审查批号：2020SJ0013）。1.2 方法1.2.1 超声检查检测仪器为法国声科 SuperSonicAixplorer超声诊断仪、迈瑞Resona7超声诊断仪，使用探头频率分别为415 MHz、39 MHz。首先要求患者以仰卧位进行检查，充分暴露其乳房、腋窝部位，涂抹耦合剂，进行常规切面扫查，记录肿块病理形态、回声、血流情况、周围组织等特征（见图1a图1b），检查完毕后切换至超声弹性成像模式，选择弹性图取样区域后，构建病灶区域及旁正常乳腺组织区域，获得SR值（见图1c图1d）。以上超声检查由两名具有 5 年以上乳腺弹性超声诊断经验的医师完成。1.2.2 病理预后指标检查 获得患者活检病理组织，在固定、石蜡包埋、切片后使用苏木精-伊红染色，随后使用光镜观察所获标本，使用SP法进行免疫组织47.87%,respectively,significantly higher than those in benign group(P0.05).ROC curve analysis showed that the AUCvalues of 2D ultrasound,SR,and their combination for breast cancer diagnosis were 0.586,0.743,and 0.761,respectively,indicating a significantly higher diagnostic efficiency of the combined detection than 2D ultrasound or SR alone(P0.05).The occurrences of spicule sign and posterior echo attenuation and SR were higher in ER-positive patients than in ER-negative patients(P0.05);lymph node metastasis was more prevalent in PR-positive patients,and their SR was higher thanPR-negative patients(P0.05);CerbB-2 positive patients had more microcalcifications and higher SR value as comparedwith CerbB-2 negative patients(P0.05).Pearman correlation analysis revealed that there were positive correlations between2D ultrasound features such as spicule sign/posterior echo attenuation and ER,lymph node metastasis and PR,microcalcification and CerbB-2,SR and ER/PR/CerbB-2(P0.05).Conclusion The combination of 2D ultrasound featuresand SR provides reliable imaging information for the diagnosis of breast cancer.The spicule sign,posterior echo attenuation,lymph node metastasis,microcalcification and SR are correlated to the pathological prognostic indicators(ER,PR,andCerbB-2).Keywords:breast cancer;two-dimensional ultrasound;ultrasonic elastic strain rate ratio;pathology中国医学物理学杂志第41卷-176染色。使用DAB染色剂，用动物血清与缓冲液代替一抗作为阴性对照。病理预后指标包括 ER、PR、CerbB-2，由专业病理医生读片。结果判读：ER、PR阳性表达，通过细胞核内有棕黄色颗粒进行判定，且根据着色的比例及程度划分反应等级，阴性：60%。判定CerbB-2是否为阳性表达时，观察细胞膜是否出现清晰的棕色着色，以此作为判定依据，若仅在ER/PR胞浆内或CerbB-2细胞核内出现着色，则不能作为阳性判断的依据5。1.3 观察指标对比良性组与恶性组二维超声特征、SR 值及ER、PR、CerbB-2阳性率，评估二维超声、SR值对乳腺癌诊断价值，分析二维超声征象、SR 值与 ER、PR、CerbB-2相关性。1.4 统计学方法采用SPSS 20.0软件进行数据分析，计量资料用均数标准差表示，采用t检验；计数资料用例（%）表示，采用2检验；绘制受试者工作特征（Receiver OperatorCharacteristic,ROC）曲线，分析二维超声、SR值对乳腺癌诊断价值，并计算曲线下面积（Area Under Curve,AUC）；二维超声征象、SR值与ER、PR、CerbB-2相关性使用Pearman相关性分析，系数用r表示，r0.4为低度线性相关，0.4r0.7为显著线性相关，0.7r1为高度线性相关。P0.05为差异有统计学意义。2 结 果2.1 良性组与恶性组二维超声特征、SR值比较恶性组二维超声特征中毛刺征、后方回声衰减、微钙化、淋巴结转移、血流丰富者及SR值明显高于良性组（P0.05），见表1。cd图1 乳腺癌二维及CDFI超声图像Figure 1 Two-dimensional and CDFI ultrasound images of breast cancer图a示“蟹足样”改变；图b示血流情况；图cd是SR值检测图ab类别毛刺征 例（%）有无后方回声衰减 例（%）有无微钙化 例（%）有无淋巴结转移 例（%）有无血流情况 例（%）丰富不丰富SR值（x s）良性组（n=171）68（37.77）103（60.23）63（36.84）108（31.16）58（33.91）113（66.09）51（29.82）120（70.18）73（42.70）98（57.64）5.272.18恶性组（n=94）59（62.77）35（27.23）58（61.70）36（28.30）50（53.20）44（46.80）49（52.12）45（47.88）63（67.02）31（32.98）14.625.412/t值12.85715.1089.33112.84114.37319.877P值0.0010.0010.0010.0010.0010.001表1 良性组与恶性组二维超声特征、SR值比较Table 1 Comparison of two-dimensional ultrasound features andstrain rate ratio(SA)between benign group and malignant group第2期 吴静,等.二维超声特征联合超声弹性应变率比值在乳腺癌中的诊断价值及与病理预后指标的相关性分析-1772.2 良性组与恶性组ER、PR、CerbB-2阳性率比较恶性组ER、PR、CerbB-2阳性率分别为59.57%、75.53%、47.87%，明显高于良性组（P0.05），见表2。2.3 二维超声、SR值对乳腺癌诊断价值绘制ROC曲线可知，联合诊断AUC值为0.761，联合检测效果明显高于两者单独检测（P0.05），见表3和图2。组别良性组（n=171）恶性组（n=94）2值P值ER12（7.01）56（59.57）87.8320.001PR9（5.26）71（75.53）142.1120.001CerbB-24（2.34）45（47.87）86.6990.001表2 良性组与恶性组ER、PR、CerbB-2阳性率比较 例（%）Table 2 Comparison of positive rates of ER,PR and CerbB-2between benign group and malignant groupcases(%)指标二维超声SR值联合诊断AUC0.5860.7430.76195%CI0.5240.6480.6780.8090.7010.821敏感度0.5630.6700.808特异度0.6090.7430.644约登指数0.1720.4180.451P值0.0060.0010.001表3 二维超声、SR值对乳腺癌的诊断价值Table 3 Diagnostic value of 2D ultrasound and SR for breast cancer2.4 不同二维超声征象、SR值的ER、PR、CerbB-2阳性表达对比ER阳性者有毛刺征、后方回声衰减、SR值高于ER阴性者（P0.05）；PR阳性者有淋巴结转移、SR值高于PR阴性者（P0.05）；CerbB-2阳性者有微钙化、SR值高于CerbB-2阴性者（P0.05），见表4。2.5 二维超声征象、SR值与ER、PR、CerbB-2相关性分析经Pearman相关性分析，二维超声征象毛刺征、后方回声衰减与ER正相关（P0.05），淋巴结转移与PR正相关（P0.05），微钙化与CerbB-2正相关，SR值与 ER、PR、CerbB-2 均为正相关（P0.05），毛刺征、后方回声衰减、微钙化、血流情况与PR无相关性（P0.05），毛刺征、后方回声衰减、淋巴结转移、血流情况与CerbB-2无相关性（P0.05），见表5。3 讨 论超声检查是乳腺癌筛查及诊断的常用手段，在常规的二维超声检查中，良性乳腺肿瘤以回声均匀、形态规则、边界清晰为主要表现，恶性肿瘤超声则多表现为形态不规则、边界不清晰、回声不均匀等特征6-7。本研究结果显示，恶性组二维超声特征中有毛刺征、后方回声衰减、微钙化、淋巴结转移、血流丰富占比明显高于良性组，与以往研究结果相符8-9。乳腺癌病变区域细胞排列异常、组织结构紊乱，超声波与正常乳腺组织交界处会形成明显的毛刺样改变，称为“毛刺征”。而乳腺癌组织内细胞密度高，对超声波的穿透能力差，因此在超声图像上呈现出后方回声衰减的现象。同时，乳腺癌组织内有的钙化物质，虽然量很少，但由于其钙化性质，超声波会对其产生回声的反射，形成微小的钙化点，因此在超声敏感度0.00.20.40.60.81.01-特异度1.00.80.60.40.20.0Model AUC:0.586(95%CI,0.524-0.648)a：二维超声对乳腺癌诊断ROC曲线图敏感度0.00.20.40.60.81.01-特异度1.00.80.60.40.20.0AUC:0.743(95%Cl,0.678-0.809)b：SR值对乳腺癌诊断ROC曲线图敏感度0.00.20.40.60.81.01-特异度1.00.80.60.40.20.0Model AUC:0.761(95%C1,0.701-0.821)c：二维超声联合SR值对乳腺癌诊断ROC曲线图图2 二维超声、SR值对乳腺癌诊断ROC曲线图Figure 2 ROC curve of 2D ultrasound and SR for breast cancer diagnosis中国医学物理学杂志第41卷-178图像上呈现出微钙化的特征。虽上述征象在一定程度上可为乳腺肿瘤性质评估提供参考，但部分乳腺良性与恶性肿瘤超声会出现重叠部分，影响诊断准确性。以往研究表明，纤维腺瘤与导管内癌超声信号均较少，且出现钙化点分布情况也相似，因此常出现导管内癌误诊为纤维腺瘤的情况10-12。病灶硬度与肿瘤性质存在密切联系。有研究发现，良性乳腺肿瘤生长为膨胀性，因此其内部组织较为疏松，硬度也较低，而恶性肿瘤多源于乳腺导管萎缩、纤维结缔组织增生的前提下生长，且生长速度快、肿瘤质地较硬，组织硬度高13-14。实时组织超声弹性成像是一种对组织力学特征成像的新型技术，通过对组织激励，提取与其相关的参数，并通过图像反映出来，对于质地坚硬的组织，其在外界激励下所产生的顺应性较小或幅度较低，质地松软的组织则相反15-16。弹性图是评估病灶性质的有效方法，良性肿瘤其弹性评分为13分，恶性则为45分，受诊断医师主观经验的影响，使得弹性评分评估可能存在一定偏倚17-18。SR是通过评价病灶组织与周围组织的硬度值之比，评价指标更为客观，在评价过程中无医生主观意识影响，评分更具有科学性及可信度19-20。在本研究中，恶性组SR值明显高于良性组，说明SR值可为乳腺癌诊断提供参考依据。通过绘制ROC曲线可知SR值联合二维超声诊断灵敏度、敏感度明显提高，两者结合可为临床提供更全面信息。乳腺癌的侵袭和转移是由多个基因调控的复杂过程，这些基因在癌细胞的生长、增殖、迁移和扩散等方面发挥着至关重要的作用。乳腺癌超声征象呈现的多样性与肿瘤生长方式密切相关21-22。ER、PR、CerbB-2在乳腺癌发生、发展中有重要作用，也是评估患者预后的有效指标23。本研究结果显示，恶性组ER、PR、CerbB-2阳性表达者明显高于良性组，而ER阳性者有毛刺征、后方回声衰减、SR值明显高于ER阴性者；PR阳性淋巴结转移、SR值高于PR阴性者；CerbB-2阳性者微钙化、SR值高于 CerbB-2阴性者，说明二维超声特征、SR值与 ER、PR、CerbB-2密切相关，根据其有效征象及SR值或可为肿瘤预后情况评估提供参考24-25。综上所述，二维超声特征联合超声SR值可为乳腺癌诊断提供全面参考信息，毛刺征、后方声衰减、类别毛刺征 例（%）有无后方回声衰减 例（%）有无微钙化 例（%）有无淋巴结转移 例（%）有无血流情况 例（%）丰富不丰富SR值（x s）ER阳性（n=68）44（64.70）24（35.30）40（58.82）28（41.18）25（36.77）43（63.23）20（29.41）48（70.59）39（57.36）29（42.64）15.492.64阴性（n=197）83（42.13）114（57.86）81（41.11）116（58.89）83（42.13）114（57.87）80（40.60）117（59.40）97（49.23）100（50.77）4.181.342/t值10.3216.3870.6032.6971.33245.571P值0.0010.0110.4370.1010.2480.001PR阳性（n=80）44（55.00）36（45.00）42（52.50）38（47.50）39（48.75）41（51.25）61（76.25）19（23.75）48（60.00）32（40.00）13.365.18阴性（n=185）83（44.87）102（55.13）79（42.70）106（57.30）69（37.30）116（62.70）39（21.08）146（78.91）88（47.56）97（52.43）5.661.872/t值2.2982.1613.03472.3463.45517.753P值0.1290.1420.0820.0010.0630.001CerbB-2阳性（n=49）25（51.02）24（48.97）29（59.19）20（40.81）31（63.26）18（36.73）21（42.86）28（57.14）27（55.10）22（44.90）14.593.15阴性（n=216）102（47.22）114（52.78）102（47.22）114（52.78）77（35.64）139（64.36）79（36.58）137（63.42）109（50.47）107（49.53）5.021.282/t值0.2311.14812.6160.6710.34434.075P值0.6310.2830.0010.4120.5570.001表4 不同二维超声征象、SR值的ER、PR、CerbB-2阳性表达对比Table 4 Comparison of positive expressions of ER,PR and CerbB-2 at different 2D ultrasonic signs and SR类别毛刺征后方回声衰减微钙化淋巴结转移血流情况SR值ERr值0.6720.6970.4110.3510.2180.758P值0.0010.0010.1350.1740.1870.001PRr值0.1020.3340.4590.7110.4200.606P值0.9520.2580.1770.0010.1850.001CerbB-2r值0.3710.4190.6500.3190.3370.677P值0.2140.1880.0010.2840.2410.001表5 二维超声征象、SR值与ER、PR、CerbB-2值的相关性分析Table 5 Correlation analysis of 2D ultrasonicsigns/SR and ER/PR/CerbB-2第2期 吴静,等.二维超声特征联合超声弹性应变率比值在乳腺癌中的诊断价值及与病理预后指标的相关性分析-179淋巴结转移、微钙化征象及SR值与患者病理预后指标ER、PR、CerbB-2之间存在相关性。超声作为无创影像学评估方法，在乳腺癌术前及非手术治疗等条件下，可为临床预测ER、PR、CerbB-2表达提供参考，或可为临床内分泌治疗、疾病预后评估提供新方向。【参考文献】1 周瑾,邢飞,樊云清,等.加速时间指数及弹性应变率比值鉴别诊断乳腺良恶性肿瘤的价值 J.临床超声医学杂志,2021,23(3):212-215.Zhou J,Xing F,Fan YQ,et al.Value of acceleration time index andelastic strain rate ratio in differential diagnosis of benign andmalignant breast tumorsJ.Journal of Ultrasound in ClinicalMedicine,2021,23(3):212-215.2 朱强,王丕琳.浆细胞性乳腺炎患者超声弹性应变率值与血清E_2,PRL,Ki-67指标表达相关性及在预后评估的应用价值 J.生物医学工程与临床,2020,24(3):272-277.Zhu Q,Wang PL.Correlation between ultrasonic elastic strain 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