超声造影对不同分子分型乳腺癌的诊断价值

左文思; 金林原; 李芬穗

doi:10.12122/j.issn.1674-4500.2019.04.01

超声造影对不同分子分型乳腺癌的诊断价值

doi: 10.12122/j.issn.1674-4500.2019.04.01

长沙市中心医院超声诊断科，湖南长沙 410000

详细信息

作者简介:
左文思，硕士，医师，E-mail：489658508@qq.com

通讯作者:
李芬穗，硕士，主任医师，E-mail：987851393@qq.com

计量
- 文章访问数: 1368
- HTML全文浏览量: 530
- PDF下载量: 26
- 被引次数: 0
出版历程
- 收稿日期: 2019-08-20
- 刊出日期: 2019-12-01

Comparative study of contrast-enhanced ultrasound in different molecular breast cancers

Department of Ultrasound Diagnosis, Changsha Central Hospital, Changsha 410000, China

摘要

摘要: 目的探讨超声造影特征及时间-强度曲线定量参数在不同分子分型乳腺癌中的差异性。方法回顾性分析142例乳腺癌患者（142个癌灶）的超声造影资料；根据雌激素受体、孕激素受体、人表皮生长因子受体-2（HER-2）、Ki-67的表达状态，将乳腺癌分为Luminal A、B型（管腔上皮型）、三阴型、HER-2过表达型4个分型，分析不同分子分型乳腺癌患者的超声造影特征及时间-强度曲线定量参数。结果Luminal A型表现为低或等增强比例为80.8%（21/26），出现放射状汇聚比例为69.2%（18/26）；Luminal B型出现低或等增强比例为60.3%（35/58），出现放射状汇聚比例为56.9%（33/58）；HER-2过表达型出现高增强比例为90.0%（27/30），内部出现灌注缺损比例为73.3%（22/30），周边有穿入血流比例为70.0%（21/30），三阴型表现为高增强比例为92.9%（26/28），增强后边界清楚比例为92.8%（26/28）。不同分子分型乳腺癌在增强边界、增强强度、穿入血流、灌注缺损比较差异均有统计学意义（P<0.05），而在增强后范围扩大、造影剂分布、造影剂增强顺序、造影模式与分子分型表达差异无统计学意义（P>0.05）；三阴型、HER-2过表达型峰值强度高于Luminal A型和Luminal B型，差异有统计学意义（P<0.05），而不同分子分型乳腺癌病灶达峰时间、平均渡越时间、曲线下面积、消除斜率比较差异均无统计学意义（P>0.05）。结论不同分子分型乳腺癌超声造影特征存在差异，可为术前乳腺癌分子分型预测提供有价值的影像学信息。
- 乳腺肿瘤 /
- 超声造影 /
- 时间-强度曲线 /
- 分子分型
Abstract: ObjectiveTo explore the differences between contrast-enhanced features and time-intensity curve quantitative parameters in different molecular types of breast cancer.MethodsWe retrospectivly analyzed 142 cases of breast cancer patients (142 tumors) by contrast-enhanced data. The estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 (HER-2), Ki-67 expression status were analyzed. The breast cancer were divided into four types: Luminal A, B (luminal epithelium), triple negative, and HER-2 overexpression. The contrast-enhanced features and time-intensity curve of breast cancer patients with different molecular classification were analyzed.ResultsLuminal type A showed a low or equal enhancement ratio of 80.8% (21/26), with a radial aggregation ratio of 69.2% (18/26). Luminal type B showed a low or equal enhancement ratio of 60.3% (35/58). The proportion of radial aggregation was 56.9% (33/58). The ratio of high enhancement of HER-2 overexpression was 90.0% (27/30), and the proportion of internal perfusion defect was 73.3% (22/30). The proportion of blood flow was 70.0% (21/30). The proportion of triple-yin showed high enhancement rate was 92.9% (26/28), and the clear ratio of enhanced boundary was 92.8% (26/28). The differences of the enhancement of borderline, enhancement intensity, perforation blood flow and perfusion defects between different molecular types of breast cancer were significant (P<0.05). But the differences of range of enhancement, contrast agent distribution, contrast agent enhancement sequence between angiographic pattern and molecular typing were not significant (P>0.05).ConclusionThere are differences in the features of contrast-enhanced ultrasound in different molecular types of breast cancer. It can provide valuable imaging information for preoperative prediction of breast cancer molecular classification.
- breast tumor /
- contrast enhanced ultrasound /
- time-intensity curve /
- molecular phenotypes

HTML全文

图 1 Luminal A型超声造影

超声造影后呈低增强，周边出现放射状汇聚

下载: 全尺寸图片幻灯片

图 2 Luminal B型超声造影

造影后呈等增强，周边出现放射状汇聚

下载: 全尺寸图片幻灯片

图 3 Her-2过表达型超声造影

超声造影后呈高增强，内部出现灌注缺损，周边有穿入血管

下载: 全尺寸图片幻灯片

图 4 三阴型超声造影

超声造影后呈高增强，边界清楚

下载: 全尺寸图片幻灯片

表 1 不同分子分型乳腺癌的超声造影特征

分子分型	增强后范围扩大		增强边界		增强强度		造影剂分布
分子分型	有	无	不清楚	清楚	高增强	低或等增强	均匀	不均匀	周边增强
管腔上皮型	79	5	75	9	28	56	28	56	12
非管腔上皮型	55	3	28	30	53	5	11	47	29
χ²	0.39		28.965		47.176		3.555
P	0.843		0.000		0.000		0.059
Luminal A型	23	3	21	5	5	21	8	18	4
Luminal B型	56	2	54	4	23	35	20	38	8
χ²	2.099		2.011		3.370		0.111
P	0.147		0.156		0.066		0.739
Luminal A型	23	3	21	5	5	21	8	18	4
三阴型	26	2	2	26	26	2	6	22	9
χ²	0.310		29.888		29.888		0.612
P	0.578		0.000		0.000		0.434
Luminal A型	23	3	21	5	5	21	8	18	4
HER-2过表达型	29	1	26	4	27	3	5	25	20
χ²	1.41		0.359		28.485		1.554.
P	0.23		0.549		0.000		0.213
Luminal B型	56	2	54	4	23	35	20	38	8
三阴型	26	2	2	26	26	2	6	22	9
χ²	0.581		61.429		21.804		1.526
P	0.446		0.000		0.000		0.217
Luminal B型	56	2	54	4	23	35	20	38	8
HER-2过表达型	29	1	26	4	27	3	5	25	20
χ²	0.001		0.991		20.426		3.086
P	0.978		0.319		0.000		0.079
三阴型	26	2	2	26	26	2	6	22
HER-2过表达型	29	1	26	4	27	3	5	25	20
χ²	0.429		36.679		0.150		0.214
P	0.513		0.000		0.698		0.644

下载: 导出CSV

分子分型	造影剂增强顺序			穿入血流		灌注缺损
分子分型	向心性	离心性	整体性	有	无	有	无
管腔上皮型	34	14	36	24	60	28	56
非管腔上皮型	22	10	26	31	27	29	29
χ²	0.094			8.948		3.996
P	0.954			0.003		0.046
Luminal A型	13	3	10	6	20	9	17
Luminal B型	21	11	26	18	40	19	39
χ²	1.608			0.557		0.028
P	0.448			0.455		0.867
Luminal A型	13	3	10	6	20	9	17
三阴型	6	4	18	10	18	7	21
χ²	4.940			1.033		0.598
P	0.085			0.310		0.439
Luminal A型	13	3	10	6	20	9	17
HER-2过表达型	16	6	8	21	9	22	8
χ²	1.253			12.283		8.449
P	0.534			0.000		0.004
Luminal B型	21	11	26	18	40	19	39
三阴型	6	4	18	10	18	7	21
χ²	2.948			0.188		0.539
P	0.229			0.664		0.463
Luminal B型	21	11	26	18	40	19	39
HER-2过表达型	16	6	8	21	9	22	8
χ²	3.078			12.166		13.082
P	0.215			0.000		0.000
三阴型	6	4	18	10	18	7	21
HER-2过表达型	16	6	8	21	9	22	8
χ²	8.733			6.842		13.533
P	0.013			0.009		0.000

下载: 导出CSV

表 2 不同分子分型乳腺癌的超声造影时间-强度曲线定量参数（Mean±SD）

分子分型	峰值强度（dB）	达峰时间（s）	平均渡越时间（s）	曲线下面积（dB/s）	消除斜率（dB/s）
Luminal A型	7.420±2.283	21.687±7.819	43.099±26.024	389.108±353.846	1.642±1.125
Luminal B型	12.199±2.410	20.405±6.885	33.937±18.641	422.502±364.747	1.836±0.935
三阴性型	17.418±3.806	18.357±7.168	33.841±21.601	493.039±312.561	2.085±1.019
HER-2过表达型	19.749±3.837	20.063±6.473	26.727±17.368	520.550±347.297	2.118±1.422
F	88.013	4.542	2.591	0.875	3.396
P	0.000	0.489	0.056	0.456	0.430

下载: 导出CSV

参考文献(29)

[1]	马丹丹, 刘坤, 齐晓伟. 2018年全球癌症统计: 乳腺癌发病和死亡人数统计[J]. 中华乳腺病杂志: 电子版, 2018, 12(6): 375-6.
[2]	Gopal RA, Arvold ND, Taghian AG, et al. Breast cancer subtype approximation, and local recurrence after breast-conserving therapy[J]. J Clin Oncol, 2012, 23(3): 290-1.
[3]	Iwamoto T, Bianchini G, Booser D, et al. Gene pathways associated with prognosis and chemotherapy sensitivity in molecular subtypes of breast cancer[J]. J Natl Cancer Inst, 2011, 103(3): 264-72. doi: 10.1093/jnci/djq524
[4]	田丽元, 陈东风, 曹长军, 等. 乳腺癌超声表现与分子生物学指标的相关性研究[J]. 中国医学影像学杂志, 2011, 19(6): 468-71, 475. doi: 10.3969/j.issn.1005-5185.2011.06.018
[5]	陈慧琪, 郭顺华, 过新民. 乳腺癌超声征象与分子分型相关性分析[J]. 中国超声医学杂志, 2015, 6(6): 498-500.
[6]	Claudon M, Cosgrove D, Albrecht T, et al. Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) - update 2008[J]. Ultraschall Med, 2008, 29(1): 28-44. doi: 10.1055/s-2007-963785
[7]	van't Veer LJ, Dai HY, van Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer[J]. Nature, 2002, 415(6871): 530-6. doi: 10.1038/415530a
[8]	Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours[J]. Nature, 2000, 406(6797): 747-52. doi: 10.1038/35021093
[9]	Park S, Koo JS, Kim MS, et al. Characteristics and outcomes according to molecular subtypes of breast cancer as classified by a panel of four biomarkers using immunohistochemistry[J]. Breast, 2012, 21(1): 50-7. doi: 10.1016/j.breast.2011.07.008
[10]	Engstrom MJ, Opdahl S, Hagen AI, et al. Molecular subtypes, histopathological grade and survival in a historic cohort of breast cancer patients[J]. Breast Cancer Res Treat, 2013, 140(3): 463-73. doi: 10.1007/s10549-013-2647-2
[11]	Zhao H, Xu R, Ouyang Q, et al. Contrast-enhanced ultrasound is helpful in the differentiation of malignant and benign breast lesions[J]. Europ J Radiol, 2010, 73(2): 288-93. doi: 10.1016/j.ejrad.2009.05.043
[12]	林韵, 王小燕, 韦海明, 等. 乳腺癌超声造影定量分析参数及增强模式与分子分型的关系[J]. 中国医学影像技术, 2014, 30(3): 406-10.
[13]	Inwald EC, Koller M, Klinkhammer-Schalke M, et al. 4-IHC classification of breast cancer subtypes in a large cohort of a clinical cancer registry: use in clinical routine for therapeutic decisions and its effect on survival[J]. Breast Cancer Res Treat, 2015, 153(3): 647-58. doi: 10.1007/s10549-015-3572-3
[14]	郑逢洋, 黄备建, 严丽霞, 等. 乳腺癌冠状面汇聚征和生物学行为指标间的相关性研究[J]. 中华超声影像学杂志, 2016, 25(6): 496-501. doi: 10.3760/cma.j.issn.1004-4477.2016.06.009
[15]	蒋珺, 陈亚青, 徐依耑, 等. 三维超声冠状面汇聚征在评估乳腺癌预后中的价值[J]. 中华超声影像学杂志, 2013, 22(10): 873-6. doi: 10.3760/cma.j.issn.1004-4477.2013.10.015
[16]	陈欣, 罗葆明, 管小凤, 等. 超微血管成像与超声造影微血管成像在乳腺病变诊断中的对比研究[J]. 中华超声影像学杂志, 2016, 25(7): 608-11. doi: 10.3760/cma.j.issn.1004-4477.2016.07.015
[17]	Tan PH, Bay BH, Yip G, et al. Immunohistochemical detection of Ki67 in breast cancer correlates with transcriptional regulation of genes related to apoptosis and cell death[J]. Mod Pathol, 2005, 18(3): 374-81. doi: 10.1038/modpathol.3800254
[18]	Park BW, Park S, Park HS, et al. Cyclooxygenase-2 expression in proliferative Ki-67-positive breast cancers is associated with poor outcomes[J]. Breast Cancer Res Treat, 2012, 133(2): 741-51. doi: 10.1007/s10549-012-1971-2
[19]	梁星宇, 王鸿凤, 李紫瑶, 等. 超声造影对不同分子分型乳腺癌鉴别诊断的初步研究[J]. 中华超声影像学杂志, 2018, 27(10): 881-6. doi: 10.3760/cma.j.issn.1004-4477.2018.10.012
[20]	Mohammed RA, Ellis IO, Lee AH, et al. Vascular invasion in breast cancer;an overview of recent prognostic developments and molecular pathophysiological mechanisms[J]. Histopathology, 2009, 55(1): 1-9. doi: 10.1111/j.1365-2559.2008.03169.x
[21]	李振洲, 罗长锐, 方凡, 等. 乳腺癌超声造影特征与C-erbB-2、p53表达的相关性研究[J]. 临床超声医学杂志, 2012, 14(9): 585-8. doi: 10.3969/j.issn.1008-6978.2012.09.003
[22]	Cichon MA, Degnim AC, Visscher DW, et al. Microenvironment influences that drive progression from breast disease to invasive breast cancer[J]. J Mammary Gland Bio Neoplasia, 2010, 15(4): 389-97. doi: 10.1007/s10911-010-9195-8
[23]	何鑫, 姜珏, 黄丽丽, 等. 超声鉴别三阴性乳腺癌与HER-2过表达型乳腺癌的初步研究[J]. 临床超声医学杂志, 2018, 20(3): 165-7. doi: 10.3969/j.issn.1008-6978.2018.03.008
[24]	张玉竹, 贾宛儒, 史俊妮, 等. 三阴性乳腺癌的超声造影特征[J]. 中国超声医学杂志, 2016, 32(11): 970-2.
[25]	胡一迪, 谢粜侠, 张辉, 等. 61例三阴性乳腺癌的临床病理特征及预后因素分析[J]. 中华内分泌外科杂志, 2018, 12(2): 118-23. doi: 10.3760/cma.j.issn.1674-6090.2018.02.008
[26]	吴芳, 成静, 马婷, 等. 不同分子分型乳腺癌的超声造影特征分析[J]. 临床超声医学杂志, 2019, 21(01): 1-4. doi: 10.3969/j.issn.1008-6978.2019.01.001
[27]	高军喜, 马方婧, 杨磊, 等. 不同分子亚型乳腺癌超声造影特征及定量参数对比研究[J]. 中国临床医学影像杂志, 2019, 30(4): 39-44.
[28]	Thielemann A, Kopczynski Z, Filas VA, et al. The determination of VEGF and MVD, among patients with primary breast cancer[J]. Pathol Oncol Res, 2008, 14(2): 137-44. doi: 10.1007/s12253-008-9040-1
[29]	Kraby MR, Kruger K, Opdahl S, et al. Microvascular proliferation in luminal A and basal-like breast cancer subtypes[J]. J Clin Pathol, 2015, 68(11): 891-7. doi: 10.1136/jclinpath-2015-203037