基底细胞样型乳腺癌的研究现状

乳腺癌在形态学、对治疗的反应及其临床过程方面具有高度异质性。基因谱表达分析将乳腺癌分为5个亚型:腺腔A型、腺腔B型、HER-2过表达型、基底细胞样型(BLBC)和正常乳腺样型,其中BLBC免疫表型独特,预后较差。本文简单介绍BLBC的流行病学特征,主要概述其组织学特征、免疫表型以及治疗和预后的研究情况。     

基底细胞样乳腺癌的诊治研究进展

基底细胞样乳腺癌是一种异质性大、恶性程度高、预后差的乳腺恶性肿瘤,其主要特征是复发率高、患者生存期短、有特殊的转移途径。它易转移到脑及内脏器官。有效的全身系统治疗只有化疗。寻找基底细胞样乳腺癌新的标志物,将成为今后基底细胞样乳腺癌治疗的新方向。     

三阴性乳腺癌与基底细胞样乳腺癌临床病理分析

目的研究CK5／6、CK14在三阴性乳腺癌（triple negativebreast carcinoma,TNBC）中的表达情况,并探讨基底细胞样乳腺癌（basal—like breast carcinoma,BLBC）与TNBC的关系。方法利用免疫组化方法从浸润性乳腺癌中筛选TNBC病例,然后利用CK5／6和CK14从TNBC中筛选出BLBC的病例,分析两者的临床与病理资料及免疫组化表达情况并复习有关文献。结果TNBC的发病率占浸润性乳腺癌的16．1％。TNBC中的CK5／6和CK14表达有正相关性（γ=0．463）。应用CK5／6、CK14从TNBC中筛选出的BLBC的百分率为54％。结论BLBC与TNBC有大部分交叉。CK5／6和CK14可以用来从TNBC中筛选出大部分的BLBC的病例。BLBC相对其他类型乳腺癌,预后不良,有必要将其从TNBC中鉴别出来。     

αB-crystallin在基底细胞样型乳腺癌中的表达及临床意义

目的 观察小热休克蛋白α-basic-crystallin（αB-crystallin）在基底细胞样型乳腺癌（BLBC）中的表达,分析其与BLBC临床病理特征的关系。方法采用免疫组织化学SP法检测αB-crystallin在108例BLBC和342例非基底细胞样型乳腺癌（NBLBC）中的表达。结果 αB-crystallin在BLBC中的阳性表达率为56.5％,高于其在NBLBC中的7.9％（P＜0.05）。αB-crystallin在BLBC中的表达与组织学分级有相关性（r=0.313,P＜0.001）,与年龄、肿瘤大小及淋巴结转移均无相关性（P＞0.05）。结论αB-crystallin可能是BLBC发生、发展的重要参与者,可作为BLBC预后不良的指标。     

基底细胞样乳腺癌的研究进展

近年来,乳腺癌已经成为威胁女性生命健康的恶性肿瘤之首。随着对乳腺癌生物学行为研究的不断深入,学者们逐渐发现原发性乳腺癌无论在组织形态、免疫表型,还是治疗敏感度上都存在着很大的差异性,是一种高度异质性的恶性肿瘤。因而,目前临床常用的组织形态学分类已经不能完全满足现有诊治的全面需求。     

凋亡相关基因p53和bax在基底细胞样乳腺癌中的表达及意义

目的:探讨p53和bax在基底细胞样乳腺癌中的表达及相互关系。方法:应用免疫组化方法检测43例基底细胞样乳腺癌(basal-like breast carcinoma,BLBC),57例非基底细胞样乳腺癌(non-BLBC),60例正常乳腺组织中p53和bax的表达。结果:p53在BLBC、non-BLBC和正常乳腺组织中的阳性表达率分别为79.07%（34/43）、52.63%（30/57）、5.00%（3/60）,两两比较,P均<0.01;bax的阳性表达率分别为20.93%（9/43）、45.61%（26/57）、76.67%（46/60）,两两比较,P均<0.01。p53和bax在BLBC中的表达水平与患者淋巴结转移情况及临床分期相关,P均<0.05,p53与bax在BLBC中的表达呈负相关（r=-0.578,P<0.01）。结论:BLBC组织中p53表达升高,bax表达降低,两者异常表达可能与BLBC的发生、发展密切相关。     

含有基底细胞样表型三阴性乳腺癌的病理特点及其临床意义

目的探讨含有基底细胞样表型(BCLT)的三阴性乳腺癌(TNBC)的病理特点。方法对徐州医学院附属宿迁医院乳腺外科2010年1月至2013年1月收治的56例TNBC,行细胞增殖核蛋白(Ki67)、抑癌基因p53、表皮生长因子受体(EGFR)、基底细胞样细胞角蛋白(CK5/6、CK17、CK14)的免疫组化检测,筛选出含有BCLT的TNBC和无BCLT的TNBC,比较两组的病理特征。结果含BCLT的TNBC患者36例(占64.29%),无BCLT的TNBC 20例。含BCLT与不含BCLT的病例相比,年龄轻、绝经前期比例高、淋巴结转移率高、病期晚、分化程度差,均P0.05。含BCLT的TNBC患者的癌组织中p53、Ki67的阳性表达率分别为91.67%及97.22%,而无BCLT的TNBC患者p53、Ki67的表达率分别为65.00%及75.00%,两组相比,差异也有统计学意义。结论含有BCLT的TNBC患者相对于无BCLT的TNBC患者,年纪轻、绝经前期比例高、淋巴结转移率高、病期晚、癌细胞分化程度差、恶性度高、预后差。对含有BCLT的TNBC患者进行基因治疗是否能提高疗效是下一步研究目标。     

Slug、E-cadherin、Vimentin及β-catenin在基底细胞样乳腺癌中的表达

[目的]观察Slug在基底细胞样乳腺癌(BLBC)中的表达情况及其与上皮间质转化(EMT)的关系.[方法]依照免疫组化表型筛选出BLBC、管腔A、管腔B/C、He卜2过表达及正常乳腺样型共147例乳腺癌,采用EnVision两步法检测各亚型中Slug、E-cadherin、Vimentin及β3-catenin的表达情况.[结果]41例BLBC中Slug、Vimentin阳性率分别为63.4％ (26/41)和39.0％(16/41).E-cadherin表达减弱率为63.4％(26/41)、β-catenin异常表达率为53.7％(21/41).BLBC组中Slug、Vimentin阳性率高于其他各亚型(P＜0.01).BLBC组中Slug表达与E-cadherin表达减弱和Vimentin表达上调存在相关性(P＜0.05).BLBC组中Slug阳性表达与组织学分级、淋巴结转移相关.[结论] EMT可能是造成BLBC特殊生物学行为的原因,并且受Slug基因表达的调节.     

基底细胞样乳腺癌免疫组化特征及其意义

[目的]探讨基底细胞样乳腺癌（BLBC）的免疫组化特征及其意义。[方法]采用免疫组化检测46例BLBC中细胞角蛋白、肌上皮标记以及EGFR、p53、ERCCl、cKit和Ki67的表达,并通过与激素受体阳性乳腺癌（HR^＋乳腺癌）的比较,分析BLBC免疫组化特点。[结果]58．7％和43．5％BLBC组织中分别表达高分子角蛋白CK5／6和CK14。32．6％、13．0％、15．2％和15．2％BLBC分别表达肌上皮标记SMA、p63、CD10和S100。高分子角蛋白和肌上皮标记表达率均高于HR^＋乳腺癌。BLBC中Vimentin、p53和Ki67阳性率分别为45．7％、60．9％和43．5％,均高于HR^＋乳腺癌。EGFR、ERCCl和cKit阳性率分别为65．2％、34．8％和30．4％,与HR^＋乳腺癌比较差异均有统计学意义。[结论]BLBC是一组可表达高分子角蛋白及肌上皮标记、细胞增殖活跃和具有侵袭倾向的乳腺癌。EGFR和ERCCl检测可用于指导临床治疗。     

乳腺基底细胞样癌的临床病理学研究进展

乳腺基底细胞样癌是新近确定的乳腺癌分子亚型,其临床表现、组织学改变及免疫表型均有其特殊性,值得深入研究,文章总结近年来乳腺基底细胞样癌的临床病理学研究进展。     

基底细胞样乳腺癌中CD109、AR的表达分析

目的:探讨基底细胞样乳腺癌(basal-like breast cancer,BLBC)的生物学特征及CD109、AR在BLBC中的表达意义。方法:对本院病理科2005年～2008年手术存档乳腺癌石蜡标本全部病例的HE组织切片进行形态学观察以确定诊断,同时采用免疫组化(S-P法)检测CD109、AR在86例BLBC和90例浸润性导管癌(invasive ductalcancer,IDC)中的表达情况。结果:BLBC具有独特的形态学特征,其癌组织异型性明显,组织学分级较高。在BLBC中CD109的阳性表达率明显高于IDC,而AR的阳性表达率则明显低于IDC;CD109在BLBC中的表达与患者年龄、肿瘤大小、肿瘤的组织学分级和淋巴结累及情况均无关,而AR在BLBC中的表达与肿瘤的组织学分级有关,与患者年龄、肿瘤大小和淋巴结累及情况无关。结论:BLBC是一组具有一定形态学特点的乳腺癌,CD109的高表达和AR的低表达在BLBC中具有明显特征,CD109不随肿瘤临床病理指标变化而具有稳定的高表达率说明了它可能是BLBC新的特异性标志物,而AR的阳性表达率随肿瘤分级升高而降低则可能与肿瘤的侵袭进展有关。     

基底样型和Luminal A型乳腺癌microRNAs表达谱的生物信息学分析

目的 对基底型和Luminal A型乳腺癌microRNAs表达谱进行分析,找出两种分子亚型乳腺癌之间差异表达的microRNAs,并对差异表达microRNAs在不同分子亚型乳腺癌中可能发挥的生物学功能进行初步探讨.方法 从公共基因芯片数据库GEO中筛选基底样型和Luminal A型乳腺癌microRNAs表达谱数据,利用BRB-arrayTools软件筛选出差异表达的microRNAs.对差异表达的microRNAs,利用TargetScan和miRDB靶基因预测软件及TarBase数据库获得可能的靶基因集.利用DAVID数据库,对差异表达micorRNAs的靶基因集进行进一步Gene Ontology和信号通路分析.结果 通过对基底样型和Luminal A型乳腺癌microRNAs表达谱分析获得54个差异表达的microRNAs(P≤0.001).相对于Luminal A亚型乳腺癌,31个microRNAs在基底样型乳腺癌中上调表达,而23个microRNAs下调表达.上调和下调表达microRNAs可能的靶基因集数目分别为4 916和3 217个.对于上调和下调microRNAs的靶基因集,Gene Ontology分析表明,两个靶基因集分别在不同的生物学过程显著富集;KEGG通路分析分别涉及了35条和39条(P≤0.05);BIOCARTA通路分析则分别涉及5条和9条(P≤0.05).结论 本研究获得了基底样型和Luminal A型乳腺癌差异表达的microRNAs,并通过靶基因功能分析获得差异表达microRNAs在两种分子亚型乳腺癌之间可能参与的不同生物学过程及信号通路,可能在不同分子亚型乳腺癌中发挥不同的调节作用.     

The Retinoblastoma Gene Undergoes Rearrangements in BRCA1-Deficient Basal-like Breast Cancer

Breast tumors from BRCA1 germ line mutation carriers typically exhibit features of the basal-like molecular subtype. However, the specific genes recurrently mutated as a consequence of BRCA1 dysfunction have not been fully elucidated. In this study, we used gene expression profiling to molecularly subtype 577 breast tumors, including 73 breast tumors from BRCA1/2 mutation carriers. Focusing on the RB1 locus, we analyzed 33 BRCA1-mutated, 36 BRCA2-mutated, and 48 non-BRCA1/2-mutated breast tumors using a custom-designed high-density oligomicroarray covering the RB1 gene. We found a strong association between the basal-like subtype and BRCA1-mutated breast tumors and the luminal B subtype and BRCA2-mutated breast tumors. RB1 was identified as a major target for genomic disruption in tumors arising in BRCA1 mutation carriers and in sporadic tumors with BRCA1 promoter methylation but rarely in other breast cancers. Homozygous deletions, intragenic breaks, or microdeletions were found in 33% of BRCA1-mutant tumors, 36% of BRCA1 promoter-methylated basal-like tumors, 13% of non-BRCA1-deficient basal-like tumors, and 3% of BRCA2-mutated tumors. In conclusion, RB1 was frequently inactivated by gross gene disruption in BRCA1 hereditary breast cancer and BRCA1-methylated sporadic basal-like breast cancer but rarely in BRCA2 hereditary breast cancer and non-BRCA1-deficient sporadic breast cancers. Together, our findings show the existence of genetic heterogeneity within the basal-like breast cancer subtype that is based upon BRCA1 status. Cancer Res; 72(16); 4028-36. ?2012 AACR.     

Basal-like乳腺癌与干细胞的研究进展

0引言目前基于基因谱将乳腺癌划分为5个分子亚型[1-2],其中Basa1-1ike乳腺癌具有独特的基因表型和形态特点,其恶性程度高,侵袭性强,临床预后差,引起了国内外肿瘤学家的高度关注.肿瘤干细胞是最近几年来肿瘤发生机制研究领域的热点,笔者就Basa1-1ike乳腺癌及其与乳腺癌干细胞相关性作一综述.     

Immunohistochemical Analysis of the Expression of Breast Markers in Basal-like Breast Carcinomas Defined as Triple Negative Cancers Expressing Keratin 5

Estrogen and progesterone receptors are possible markers for suggesting a mammary origin of metastatic carcinoma, but are useless in cases of triple negative breast cancers (TNBC). Five other potential markers of breast origin were investigated on tissue microarrays in a series of TNBCs showing keratin 5 expression, consistent with a basal-like phenotype. GATA-3 staining was observed in 82 of 115 triple negative cases (71.3%) including 23 cases with >5% staining. Mammaglobin staining was detected in 30 cases (26.0%) including 12 with >5% staining. GCDFP-15 was seen in 23 cases (20.0%) including 9 with >5% staining. NY-BR-1 positivity was present in 7 cases (6.0%) including 3 patients with >5% staining. BCA-225 staining was observed in 74 cases (64.3%); however this latter marker lacks also specificity owing to the reported widespread staining in other malignancies. GATA-3, mammaglobin and GCDFP-15 coexpression was seen in one case (0.9%), whereas GATA-3 and mammaglobin or mammaglobin and GCDFP-15 coexpression was present in 2 and 2 cases (1.7%), respectively. Using at least 5% staining as cut-off, the expression of any of the last 4 markers was 34.7%. The expression of GATA-3, mammaglobin, GCDFP-15 and NY-BR-1 is lower in TNBC-s than in breast carcinomas in general, and this may be even lower in basal-like carcinomas. Although these markers are not fully specific, by using them, a subset of basal-like TNBC-s can be identified as of mammary origin. However, a substantial proportion will not show any staining with any of these markers.     

组学技术在胶质瘤分子分类方面应用研究进展

胶质瘤传统病理学的分类分级主要基于细胞水平的认识,而缺乏对胶质瘤分子学特征的认识。随着分子生物学的发展,尤其是基因组学和蛋白质组学技术的发展,人们逐渐肯定了髓母细胞瘤起源于小脑颗粒细胞,少枝胶质细胞瘤因按其基因表达谱的差异可进一步进行分类,依据胶质细胞瘤基因或蛋白的表达差异可对胶质细胞瘤进行分级及预后预测,并可对胶质母细胞瘤进行进一步分类。组学技术的发展扩大了检测胶质瘤分子缺陷的数目,推动了胶质瘤分子分类方法的发展。     

Evaluation of Therapeutic Target Gene Expression Based on Residual Cancer Burden Classification After Neoadjuvant Chemotherapy for HER2-Negative Breast Cancer

IntroductionPatients with residual disease usually have a poor prognosis after neoadjuvant chemotherapy for breast cancer. The aim of this study was to explore therapeutic targets and potential additional adjuvant treatments for patients with residual disease after standard neoadjuvant chemotherapy.Patients and MethodsWe retrieved publicly available complementary DNA microarray data from 399 human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer samples from patients who underwent standard neoadjuvant chemotherapy. We analyzed the messenger RNA (mRNA) expression levels of key breast cancer markers and therapeutic target genes according to residual cancer burden (RCB) classification: RCB-0/I, RCB-II, and RCB-III.ResultsAmong hormone receptor–positive samples, there were more luminal A tumors by PAM50 (Prediction Analysis of Microarray 50 [Prosigna], aka Prosigna Breast Cancer Prognostic Gene Signature Assay) in RCB-III than in RCB-0/I and RCB-II (P < .01). The mRNA expressions of ESR1 and PGR were significantly higher, and that of MKI67 was lower in RCB-II and RCB-III than in RCB-0/I. The mRNA expression of cyclin D1 was up-regulated in RCB-III and that of CDKN2A was down-regulated in RCB-III (P = .027 and < .01). Among triple-negative (TN) samples, RCB-III had higher clinical stage and more lymph node–positive samples than RCB-0/1 and RCB-II (P < .01). In both subtypes, VEGF-C expression was significantly higher in RCB-III than in RCB-0/I and RCB-II.ConclusionIn hormone receptor–positive breast cancer, biological features such as luminal A were associated with RCB; this trend was not observed in TN breast cancer. Further, some targeted therapies should be tested as new strategies after standard neoadjuvant chemotherapy in future clinical trials.     

Basal-like型乳腺癌临床特征与生存分析

目的分析Basal-like型乳腺癌所占比例、临床特征以及生存情况,为Basal-like型乳腺癌临床诊治提供参考依据。方法回顾性分析我院经手术治疗、资料完整、经病理确诊的女性乳腺癌患者171例。Basal-like型乳腺癌的判定采用Nielsen标准。比较Basal-like型乳腺癌与非Basal-like型乳腺癌的临床病理特征、复发转移及生存情况。结果Basal-like型乳腺癌26例,占15.3%。Basal-like型乳腺癌具有组织学分级高（Basal-like型与非Basal-like型乳腺癌组织学分级Ⅲ级的比例分别为：69.23%和3034%,P＜0.001）,淋巴结转移阳性率低（34.62%和58.62%,P=0.023）,淋巴结转移率低（41.38%和65.38%,P=0.038）的特点。与非Basal-like型乳腺癌相比,Basal-like型乳腺癌肺转移发生率较高（15.38%和3.45%,P=0.012）。Basal-like型乳腺癌和非Basal-like型乳腺癌的5年生存率分别为703%和87.9%（P=0.042）,5年无病生存率分别为59.5%和80.3%（P=0.013）。结论本组患者并没有发现回、汉族患者Basal-like型乳腺癌的发病率差别。本组Basal-like型乳腺癌患者具有组织学分级高、淋巴结转移阳性率低、淋巴结转移率低、易于发生肺转移和预后较差的特点。