浸润性三阴性乳腺癌超声特征的临床、病理学及免疫组织化学基础
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摘要
背景与目的:三阴性乳腺癌(triple-negative breast cancer,TNBC)细胞增殖程度高,有明显的肿瘤异质性,缺乏针对性治疗药物,是恶性程度最高、预后最差的乳腺癌分子分型。超声是TNBC筛查和鉴别诊断的重要影像学方法之一。TNBC的超声图像特征表现出明显的变异性。该研究旨在探讨临床、病理学及免疫组织化学因素对TNBC超声图像特征的影响。方法:回顾性分析119例手术后经病理学检查证实的浸润性TNBC患者的术前超声图像、临床及病理学资料。2名具有5年以上临床经验的超声科医师对乳腺癌肿块超声图像进行特征分析与评估,评估内容包括肿块的方位、形态、边缘、内部回声、后方回声改变及钙化。按照患者年龄、肿瘤大小、病理组织学级别、Ki-67表达水平及人类表皮生长因子受体2(human epidermal growth factor receptor-2,HER2)评分将患者分组,以研究这些因素对TNBC超声图像特征的影响。结果:浸润性TNBC的超声特征与患者年龄、肿块大小、病理学分级、Ki-67表达水平及HER2评分相关:患者年龄影响肿块的后方回声(P=0.002),肿块大小影响肿块边缘是否毛刺成角(P=0.025),病理学分级影响肿块的形态(P=0.008)及后方回声(P=0.044),Ki-67表达影响肿块的形态(P=0.042)、边缘是否毛刺成角(P=0.005)及后方回声(P=0.005),HER2评分影响钙化的发生率(P=0.024)。结论:浸润性TNBC的超声声像图特征与患者年龄、肿块大小、病理学分级、Ki-67增殖水平及HER2评分有关。了解TNBC的超声特征及变异性相关的临床、病理学及免疫组织化学基础,可辅助早期诊断和提高诊断准确性。
Background and purpose: While being recognized as a heterogeneous disease, triple-negative breast cancer (TNBC) is associated with aggressive biological property, a lack of targeted therapy and poor prognosis. Ultrasonography is one of the most important imaging methods for screening and differential diagnosis of TNBC. The sonographic features of TNBC show great variability. The primary objective of the present study was to evaluate the clinicopathological factors associated with sonographic appearances of invasive TNBC. Methods: With the ethical approval, 119 patients who were pathologically confirmed as having invasive TNBC were retrospectively reviewed for ultrasound, clinical and pathological data. Two ultrasound physicians with at least 5 years' experiences for breast diseases reviewed all ultrasound images and evaluated the sonographic features which included orientation, shape, margin, internal echo pattern, posterior acoustic pattern and calcification. Patients were grouped according to age, tumor size, histological grade, Ki-67 proliferation level and human epidermal growth factor receptor-2 (HER2) score to investigate the effects of these factors on the ultrasonographic characteristics of TNBC. The effects of clinicopathological factors on the sonographic features of TNBC were studied. Results: The sonographic features of TNBC were associated with patient age, tumor size, histological grade, Ki-67 proliferation level and HER2 score. Age of patient affected the posterior acoustic pattern (P=0.002). Tumor size affected the presence of angular or spiculated margin (P=0.025). Histological grade affected tumor shape (P=0.008) and posterior acoustic pattern (P=0.044). Ki-67 level affected the tumor shape (P=0.042), presence of angular or spiculated margin (P=0.005) and posterior acoustic pattern (P=0.005). HER2 score affected the incidence of calcification inside TNBC (P=0.024). Conclusion: The sonographic features of TNBC are related to the patient's age, tumor size, histological grade, Ki-67 proliferation level and HER2 score. Understanding the clinicopathological and immunohistochemical basis of sonographic characteristics and variability of TNBC is expected to assist early and accurate diagnosis of TNBC.
Background and purpose: While being recognized as a heterogeneous disease, triple-negative breast cancer (TNBC) is associated with aggressive biological property, a lack of targeted therapy and poor prognosis. Ultrasonography is one of the most important imaging methods for screening and differential diagnosis of TNBC. The sonographic features of TNBC show great variability. The primary objective of the present study was to evaluate the clinicopathological factors associated with sonographic appearances of invasive TNBC. Methods: With the ethical approval, 119 patients who were pathologically confirmed as having invasive TNBC were retrospectively reviewed for ultrasound, clinical and pathological data. Two ultrasound physicians with at least 5 years' experiences for breast diseases reviewed all ultrasound images and evaluated the sonographic features which included orientation, shape, margin, internal echo pattern, posterior acoustic pattern and calcification. Patients were grouped according to age, tumor size, histological grade, Ki-67 proliferation level and human epidermal growth factor receptor-2 (HER2) score to investigate the effects of these factors on the ultrasonographic characteristics of TNBC. The effects of clinicopathological factors on the sonographic features of TNBC were studied. Results: The sonographic features of TNBC were associated with patient age, tumor size, histological grade, Ki-67 proliferation level and HER2 score. Age of patient affected the posterior acoustic pattern (P=0.002). Tumor size affected the presence of angular or spiculated margin (P=0.025). Histological grade affected tumor shape (P=0.008) and posterior acoustic pattern (P=0.044). Ki-67 level affected the tumor shape (P=0.042), presence of angular or spiculated margin (P=0.005) and posterior acoustic pattern (P=0.005). HER2 score affected the incidence of calcification inside TNBC (P=0.024). Conclusion: The sonographic features of TNBC are related to the patient's age, tumor size, histological grade, Ki-67 proliferation level and HER2 score. Understanding the clinicopathological and immunohistochemical basis of sonographic characteristics and variability of TNBC is expected to assist early and accurate diagnosis of TNBC.
引文
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[14]魏晏平,李智贤,曾健,等.常规超声结合弹性成像对三阴性乳腺癌的诊断价值[J].中国超声医学杂志,2012,28(6):508-510.
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[17]ELSAWAF Z,SINN H P,ROM J,et al.Biological subtypes of triple-negative breast cancer are associated with distinct morphological changes and clinical behaviour[J].Breast,2013,22(5):986-992.
[18]JIANG Y Z,LIU Y R,XU X E,et al.Transcriptome analysis of triple-negative breast cancer reveals an integrated mRNA-lncRNA signature with predictive and prognostic value[J].Cancer Res,2016,76(8):2105-2114.
[19]LIU Y R,JIANG Y Z,XU X E,et al.Comprehensive transcriptome analysis identifies novel molecular subtypes and subtype-specific RNAs of triple-negative breast cancer[J].Breast Cancer Res,2016,18(1):33.
[20]BURSTEIN M D,TSIMELZON A,POAGE G M,et al.Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer[J].Clin Cancer Res,2015,21(7):1688-1698.
[21]LEHMANN B D,BAUER J A,CHEN X,et al.Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies[J].J Clin Invest,2011,121(7):2750-2767.
[22]肖毅,江一舟,邵志敏.乳腺癌的精准医学研究[J].复旦学报(医学版),2017,44(6):765-772.
[23]CELEBI F,PILANCI K N,ORDU C,et al.The role of ultrasonographic findings to predict molecular subtype,histologic grade,and hormone receptor status of breast cancer[J].Diagn Interv Radiol,2015,21(6):448-453.
[24]ZHENG F Y,LU Q,HUANG B J,et al.Imaging features of automated breast volume scanner:correlation with molecular subtypes of breast cancer[J].Eur J Radiol,2017,86:267-275.
[25]黄小莉.三阴性乳腺癌的超声影像学研究进展[J].中国临床新医学,2017,10(6):600-602.
[26]唐石初,王志远,欧阳涛.三阴性乳腺癌超声特征探讨[J].中国医师杂志,2015,17(8):1197-1199.
[27]李佳伟,时兆婷,郭翌,等.超声影像组学对浸润性乳腺癌激素受体表达预测价值的探索性研究[J].肿瘤影像学,2017,26(2):128-135.
[28]STAVROS A T.The breast.In:RUMACK C M,WILSON S R,CHARBONEAU J W,et al,eds.Diagnostic ultrasound[M].Philadelphia,PA:Elsevier Mosby,2011.
[29]COSTANTINI M,BELLI P,BUFI E,et al.Association between sonographic appearances of breast cancers and their histopathologic features and biomarkers[J].J Clin Ultrasound,2016,44(1):26-33.
[30]AHO M,IRSHAD A,ACKERMAN S J,et al.Correlation of sonographic features of invasive ductal mammary carcinoma with age,tumor grade,and hormone-receptor status[J].JClin Ultrasound,2013,41(1):10-17.
[31]KIM S H,SEO B K,LEE J,et al.Correlation of ultrasound findings with histology,tumor grade,and biological markers in breast cancer[J].Acta Oncol,2008,47(8):1531-1538.
[32]TAMAKI K,ISHIDA T,MIYASHITA M,et al.Correlation between mammographic findings and corresponding histopathology:potential predictors for biological characteristics of breast diseases[J].Cancer Sci,2011,102(12):2179-2185.
[33]LAMB P M,PERRY N M,VINNICOMBE S J,et al.Correlation between ultrasound characteristics,mammographic findings and histological grade in patients with invasive ductal carcinoma of the breast[J].Clin Radiol,2000,55(1):40-44.
[34]TAN P H,BAY B H,YIP G,et al.Immunohistochemical detection of Ki-67 in breast cancer correlates with transcriptional regulation of genes related to apoptosis and cell death[J].Mod Pathol,2005,18(3):374-381.
[35]PARK B W,PARK S,PARK H S,et al.Cyclooxygenase-2expression in proliferative ki-67-positive breast cancers is associated with poor outcomes[J].Breast Cancer Res Treat,2012,133(2):741-751.
[36]ZHANG L,LI J,XIAO Y,et al.Identifying ultrasound and clinical features of breast cancer molecular subtypes by ensemble decision[J].Sci Rep,2015,5:11085.
[37]SEO B K,PISANO E D,KUZIMAK C M,et al.Correlation of HER2/neu overexpression with mammography and age distribution in primary breast carcinomas[J].Acad Radiol,2006,13(10):1211-1218.
[38]MOASSER M M.The oncogene HER2:its signaling and transforming functions and its role in human cancer pathogenesis[J].Oncogene,2007,26(45):6469-6487.
[2]MORRIS G J,NAIDU S,TOPHAM A K,et al.Differences in breast carcinoma characteristics in newly diagnosed AfricanAmerican and Caucasian patients:a single-institution compilation compared with the National Cancer Institute’s Surveillance,Epidemiology,and End results database[J].Cancer,2007,110(4):876-884.
[3]GOLDHIRSCH A,WINER E P,COATES A S,et al.Personalizing the treatment of women with early breast cancer:highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013[J].Ann Oncol,2013,24(9):2206-2223.
[4]LI C Y,ZHANG S,ZHANG X B,et al.Clinicopathological and prognostic characteristics of triple-negative breast cancer(TNBC)in Chinese patients:a retrospective study[J].Asian Pac J Cancer Prev,2013,14(6):3779-3784.
[5]LIAO H Y,ZHANG W W,SUN J Y,et al.The clinicopathological features and survival outcomes of different histological subtypes in triple-negative breast cancer[J].JCancer,2018,9(2):296-303.
[6]BAUER K R,BROWN M,CRESS R D,et al.Descriptive analysis of estrogen receptor(ER)-negative,progesterone receptor(PR)-negative,and HER2-negative invasive breast cancer,the so-called triple-negative phenotype:a populationbased study from the California Cancer Registry[J].Cancer,2007,109(9):1721-1728.
[7]RAKHA E A,REIS-FILHO J S,ELLIS I O.Basal-like breast cancer:a critical review[J].J Clin Oncol,2008,26(15):2568-2581.
[8]CAREY L A,PEROU C M,LIVASY C A,et al.Race,breast cancer subtypes,and survival in the Carolina Breast Cancer Study[J].JAMA,2006,295(21):2492-2502.
[9]YANG Q,LIU H Y,LIU D,et al.Ultrasonographic features of triple-negative breast cancer:a comparison with other breast cancer subtypes[J].Asian Pac J Cancer Prev,2015,16(8):3229-3232.
[10]SANNOMIYA N,HATTORI Y,UEDA N,et al.Correlation between ultrasound findings of tumor margin and clinicopathological findings in patients with invasive ductal carcinoma of the breast[J].Yonago Acta Med,2016,59(2):163-168.
[11]UEMATSU T,KASAMI M,YUEN S.Triple-negative breast cancer:correlation between MR imaging and pathologic findings[J].Radiology,2009,250(3):638-647.
[12]BOISSERIE-LACROIX M,MACGROGAN G,DEBLED M,et al.Triple-negative breast cancers:associations between imaging and pathological findings for triple-negative tumors compared with hormone receptor-positive/human epidermal growth factor receptor-2-negative breast cancers[J].Oncologist,2013,18(7):802-811.
[13]WOJCINSKI S,STEFANIDOU N,HILLEMANNS P,et al.The biology of malignant breast tumors has an impact on the presentation in ultrasound:an analysis of 315 cases[J].BMCWomens Health,2013,13:47.
[14]魏晏平,李智贤,曾健,等.常规超声结合弹性成像对三阴性乳腺癌的诊断价值[J].中国超声医学杂志,2012,28(6):508-510.
[15]MENDELSON E B,B HM-V LEZ M,BERG W A.ACR BI-RADS~? ultrasound.ACR BI-RADS~? atlas,breast imaging reporting and data system[M].Reston:American College of Radiology,2013.
[16]CHEN W,ZHENG R,BAADE P D,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-132.
[17]ELSAWAF Z,SINN H P,ROM J,et al.Biological subtypes of triple-negative breast cancer are associated with distinct morphological changes and clinical behaviour[J].Breast,2013,22(5):986-992.
[18]JIANG Y Z,LIU Y R,XU X E,et al.Transcriptome analysis of triple-negative breast cancer reveals an integrated mRNA-lncRNA signature with predictive and prognostic value[J].Cancer Res,2016,76(8):2105-2114.
[19]LIU Y R,JIANG Y Z,XU X E,et al.Comprehensive transcriptome analysis identifies novel molecular subtypes and subtype-specific RNAs of triple-negative breast cancer[J].Breast Cancer Res,2016,18(1):33.
[20]BURSTEIN M D,TSIMELZON A,POAGE G M,et al.Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer[J].Clin Cancer Res,2015,21(7):1688-1698.
[21]LEHMANN B D,BAUER J A,CHEN X,et al.Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies[J].J Clin Invest,2011,121(7):2750-2767.
[22]肖毅,江一舟,邵志敏.乳腺癌的精准医学研究[J].复旦学报(医学版),2017,44(6):765-772.
[23]CELEBI F,PILANCI K N,ORDU C,et al.The role of ultrasonographic findings to predict molecular subtype,histologic grade,and hormone receptor status of breast cancer[J].Diagn Interv Radiol,2015,21(6):448-453.
[24]ZHENG F Y,LU Q,HUANG B J,et al.Imaging features of automated breast volume scanner:correlation with molecular subtypes of breast cancer[J].Eur J Radiol,2017,86:267-275.
[25]黄小莉.三阴性乳腺癌的超声影像学研究进展[J].中国临床新医学,2017,10(6):600-602.
[26]唐石初,王志远,欧阳涛.三阴性乳腺癌超声特征探讨[J].中国医师杂志,2015,17(8):1197-1199.
[27]李佳伟,时兆婷,郭翌,等.超声影像组学对浸润性乳腺癌激素受体表达预测价值的探索性研究[J].肿瘤影像学,2017,26(2):128-135.
[28]STAVROS A T.The breast.In:RUMACK C M,WILSON S R,CHARBONEAU J W,et al,eds.Diagnostic ultrasound[M].Philadelphia,PA:Elsevier Mosby,2011.
[29]COSTANTINI M,BELLI P,BUFI E,et al.Association between sonographic appearances of breast cancers and their histopathologic features and biomarkers[J].J Clin Ultrasound,2016,44(1):26-33.
[30]AHO M,IRSHAD A,ACKERMAN S J,et al.Correlation of sonographic features of invasive ductal mammary carcinoma with age,tumor grade,and hormone-receptor status[J].JClin Ultrasound,2013,41(1):10-17.
[31]KIM S H,SEO B K,LEE J,et al.Correlation of ultrasound findings with histology,tumor grade,and biological markers in breast cancer[J].Acta Oncol,2008,47(8):1531-1538.
[32]TAMAKI K,ISHIDA T,MIYASHITA M,et al.Correlation between mammographic findings and corresponding histopathology:potential predictors for biological characteristics of breast diseases[J].Cancer Sci,2011,102(12):2179-2185.
[33]LAMB P M,PERRY N M,VINNICOMBE S J,et al.Correlation between ultrasound characteristics,mammographic findings and histological grade in patients with invasive ductal carcinoma of the breast[J].Clin Radiol,2000,55(1):40-44.
[34]TAN P H,BAY B H,YIP G,et al.Immunohistochemical detection of Ki-67 in breast cancer correlates with transcriptional regulation of genes related to apoptosis and cell death[J].Mod Pathol,2005,18(3):374-381.
[35]PARK B W,PARK S,PARK H S,et al.Cyclooxygenase-2expression in proliferative ki-67-positive breast cancers is associated with poor outcomes[J].Breast Cancer Res Treat,2012,133(2):741-751.
[36]ZHANG L,LI J,XIAO Y,et al.Identifying ultrasound and clinical features of breast cancer molecular subtypes by ensemble decision[J].Sci Rep,2015,5:11085.
[37]SEO B K,PISANO E D,KUZIMAK C M,et al.Correlation of HER2/neu overexpression with mammography and age distribution in primary breast carcinomas[J].Acad Radiol,2006,13(10):1211-1218.
[38]MOASSER M M.The oncogene HER2:its signaling and transforming functions and its role in human cancer pathogenesis[J].Oncogene,2007,26(45):6469-6487.