任新瑜;袁礼;沈松杰;吴焕文;陆俊良;梁智勇;
REN Xin-yu;YUAN Li;SHEN Song-jie;WU Huan-wen;LU Jun-liang;LIANG Zhi-yong;Department of Pathology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College;Department of Breast Surgery,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College;

• 1:中国医学科学院北京协和医学院北京协和医院病理科
• 2:中国医学科学院北京协和医学院北京协和医院乳腺外科

摘要(Abstract)：

目的探讨联合检测CK5/6、CK14和表皮生长因子受体(epidermal growth factor receptor,EGFR)对基底样三阴乳腺癌的诊断价值。方法北京协和医院2000年1月至2011年12月经组织病理学证实的115例三阴乳腺癌患者,收集其临床及病理资料。应用免疫组织化学法检测所有石蜡标本中CK5/6,CK14和EGFR的表达,以此判定是否为基底样三阴乳腺癌。以三者联合检测结果作为金标准,计算CK5/6,CK14和EGFR单独检测、两两联合检测的敏感性和特异性。进一步分析基底样三阴乳腺癌和非基底样三阴乳腺癌在年龄、肿瘤大小、组织学类型等临床及病理特征方面的差异。结果115例三阴乳腺癌患者平均患病年龄为(50.7±13.6)岁。免疫组织化学结果显示,单独检测CK5/6,基底样三阴乳腺癌阳性率为29.6%(34/115),CK14为21.7%(18/83),EGFR为60.9%(70/115)。CK14,CK5/6和EGFR三者联合检测阳性率为67.8%(78/115)。将三者联合检测的阳性例数作为金标准,则EGFR与CK5/6联合检测敏感性及特异性分别可达98.7%及100%。基底样三阴乳腺癌与非基底样三阴乳腺癌在组织学类型、分级,淋巴结转移情况,死亡率方面差异有统计学意义(P均<0.05),基底样三阴乳腺癌总生存期显著缩短(HR=0.363,95%CI:0.139~0.947)。结论 CK14、CK5/6和EGFR联合检测能够标识出最多数量的基底样三阴乳腺癌。基底样三阴乳腺癌预后比非基底样三阴乳腺癌预后更差,病理识别很重要。
Objective To investigate the value of combined detection of CK5/6,CK14 and epidermal growth factor receptor( EGFR) in diagnosing basal-like subtype triple negative breast cancer( TNBC). Methods The clinical and pathological data of 115 patients diagnosed with TNBC were recorded from January 2000 to December 2011. The expression of CK5/6,CK14 and EGFR were detected with immunohistochemical methods using paraffin specimens. Combined detection result of the three markers was used as gold standard,then the sensitivity and specificity of CK5/6,CK14 and EGFR were detected by single marker and two combined assays. The differences between basal-like and non basal-like subtype TNBC in age,tumor size,tumor histologi-cal type and other clinicopathological issues were compared. Results The mean age of 115 patients with TNBC was( 50. 7 ± 13. 6) years. Immunhistochemical result showed that single marker positivity was 29. 6 %( 34/115),21. 7%( 18/83),and 60. 9%( 70/115) for CK5/6,CK14,and EGFR,respectively. Combined detection of the three markers,the positive rate was 67. 8 %( 78/115). Taking three markers combination as a golden standard,the sensitivity and specificity of EGFR and CK5/6 combination were 98. 7 % and100 %. There were significant differences between basal-like and non basal-like subtype TNBC in histological type,tumor grade,lymph node metastasis and mortality( all P < 0. 05). Survival analysis showed that the overall survival period of basal-like subtype TNBC was significant shortened( HR = 0. 363,95 % CI: 0. 139~ 0. 947). Conclusions Combined detection of CK5/6,CK14 and EGFR could identifiy the largest number of basal-like subtype TNBC. The prognosis of basal-like subtype TNBC is worse than that of non basal-like subtype TNBC,and it is important to identify the subtype.

关键词(KeyWords)： 三阴乳腺癌;基底样亚型;CK5/6;CK14;受体,表皮生长因子
triple-negative breast cancer;basal-like subtype;CK5/6;CK14;epidermal growth factor receptor

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 任新瑜;袁礼;沈松杰;吴焕文;陆俊良;梁智勇;
REN Xin-yu;YUAN Li;SHEN Song-jie;WU Huan-wen;LU Jun-liang;LIANG Zhi-yong;Department of Pathology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College;Department of Breast Surgery,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College;

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参考文献(References)：

• [1]Perou CM,Sorlie T,Eisen MB,et al.Molecular portraits of human breast tumours[J].Nature,2000,406:747-752.
• [2]Sorlie T,Perou CM,Tibshirani R,et al.Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications[J].Proc Natl Acad Sci USA,2001,98:10869-10874.
• [3]Sotiriou C,Wirapati P,Loi S,et al.Gene expression profiling in breast cancer:understanding the molecular basis of histologic grade to improve prognosis[J].J Natl Cancer Inst,2006,98:262-272.
• [4]Sorlie T,Tibshirani R,Parker J,et al.Repeated observation of breast tumor subtypes in independent gene expression data sets[J].Proc Natl Acad Sci USA,2003,100:8418-8423.
• [5]Sotiriou C,Neo SY,Mc Shane LM,et al.Breast cancer classification and prognosis based on gene expression profiles from a population based study[J].Proc Natl Acad Sci USA,2003,100:10393-10398.
• [6]Rakha EA,Ellis IO.Triple-negative/basal-like breast cancer:review[J].Pathology,2009,41:40-47.
• [7]Nielsen TO,Hsu FD,Jensen K,et al.Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma[J].Clin Cancer Res,2004,10:5367-5374.
• [8]Leidy J,Khan A,Kandil D.Basal-like breast cancer:update on clinicopathologic,immunohistochemical and moleculr features[J].Arch Pathol Lab Med,2014,138:37-43.
• [9]National Health Service Breast Screening Programme(NHSBSP)and The Royal College of Pathologists.Pathology Reporting of Breast Disease[M].Sheffield:NHSBSP and The Royal College of Pathologists,2005:58.
• [10]Weigelt B,Baehner FL,Reis-Filho JS.The contribution of gene expression profilingto breast cancer classification,prognostication and prediction:a retrospective of the last decade[J].J Pathol,2010,220:263-280.
• [11]Nielsen TO,Hsu FD,Jensen K,et al.Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma[J].Clin Cancer Res,2004,10:5367-5374.
• [12]Cheang MC,Voduc D,Bajdik C,et al.Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype[J].Clin Cancer Res,2008,14:1368-1376.
• [13]Badve S,Dabbs DJ,Schnitt SJ,et al.Basal-like and triplenegative breast cancers:a critical review with an emphasis on the implications for pathologists and oncologists[J].Mod Pathol,2011,24:157-167.
• [14]Perou CM.Molecular Stratification of Triple-Negative Breast Cancers[J].Oncologist,2011,16:61-70.
• [15]Kim MJ,Ro JY,Ahn SH,et al.Clinicopathologic significance of the basal-like subtype of breast cancer:a comparison with hormone receptor and Her2/neu-overexpressing phenotypes[J].Hum Pathol,2006,37:1217-1226.
• [16]Livasy CA,Karaca G,Nanda R,et al.Phenotypic evaluation of the basallike subtype of invasive breast carcinoma[J].Mod Pathol,2006,19:264-271.
• [17]Rakha EA,Elsheikh SE,Aleskandarany MA,et al.Triplenegative breast cancer:distinguishing between basal and nonbasal subtypes[J].Clin Cancer Res,2009,15:2302-2310.
• [18]Jumppanen M,Gruvberger-Saal S,Kauraniemi P,et al.Basal-like phenotype is not associated with patient survival in estrogen-receptornegative breast cancers[J].Breast Cancer Res,2007,9:R16.
• [19]Bertucci F,Finetti P,Cervera N,et al.How basal are triple-negative breast cancers?[J].Int J Cancer,2008,123:236-240.
• [20]Tischkowitz M,Brunet JS,Begin LR,et al.Use of immunohistochemical markers can refine prognosis in triple negative breast cancer[J].BMC Cancer,2007,7:134.
• [21]Bidard FC,Conforti R,Boulet T,et al.Does triple-negative phenotype accurately identify basal-like tumour?An immunohistochemical analysis based on 143‘triple-negative’breast cancers[J].Ann Oncol,2007,18:1285-1286.
• [22]Tan DS,Marchio C,Jones RL,et al.Triple negative breast cancer:molecular profiling and prognostic impact in adjuvant anthracyclinetreated patients[J].Breast Cancer Res Treat,2008,111:27-44.