细胞角蛋白20的表达与乳腺癌进展、转移及预后的相关性

目的: 探讨细胞角蛋白20(CK20)在乳腺癌组织中的表达及其与乳腺癌进展、转移和预后的相关性.方法: 选取乳腺癌患者86例,以20例乳腺良性肿瘤组织作为对照,应用免疫组织化学染色方法检测CK20的表达,并分析其与乳腺癌临床病理特征及预后的关系.结果: CK20在乳腺癌组织中的阳性表达率为80.23%(69/86),明显高于在乳腺良性肿瘤中的表达[20.00%(4/20),P<0.01].CK20的表达与乳腺癌组织学分级(P<0.05) 和病理类型(P<0.01) 有关,与TNM 分期(r=0.86,P<0.05)、淋巴结转移(r=0.73,P<0.05) 和HER-2 (r=0.69,P<0.05) 呈正相关,与ER (r=-0.58,P<0.05) 呈负相关.CK20阳性表达组和CK20阴性表达组的5年生存率分别为38.46%(25/65)和66.67%(10/15),差异有统计学意义(P<0.01).结论: CK20与乳腺癌的进展、转移有关,作为新的乳腺癌标记物,有一定的临床实际应用价值.     

COX-2、VEGF在乳腺癌组织中的表达及临床意义

目的探讨血管内皮生长因子(VEGF)和环氧化酶-2(COX-2)在乳腺癌组织中的表达及其与临床病理特征之间的关系。方法应用免疫组化S-P法检测不同乳腺组织中VEGF和COX-2的表达情况。结果VEGF、COX-2在乳腺导管癌组织中的表达明显上调,与其在正常乳腺组织、纤维腺瘤组织中的表达相比差异显著(P<0.01)。VEGF、COX-2在乳腺浸润性导管癌中的阳性表达率高于其在乳腺导管癌中的阳性表达率。两组中COX-2的表达有显著性差异(77.1%vs40%,P<0.05),VEGF的表达无显著性差异(80.0%vs70%,P>0.05)。VEGF在乳腺浸润性导管癌的阳性表达与其临床分期、淋巴结转移密切相关(P<0.05,P<0.01),与肿瘤大小无关(P>0.05)。COX-2在乳腺浸润性导管癌中的阳性表达与其临床分期、淋巴结转移及肿瘤大小均无关(P>0.05)。VEGF、COX-2在乳腺导管癌中的表达呈正相关(r=0.98,P<0.05)。结论VEGF、COX-2的高表达在乳腺癌的发生发展过程中起重要的作用,可作为重要的生物学标志。     

乳腺癌和非癌组织中Syk、survivin和Ki-67的表达及其相关性

目的 探讨乳腺癌和非癌组织中Syk、survivin和Ki-67的表达及其相互关系.方法 应用免疫组化SP法检测52例乳腺浸润性导管癌和39例非癌组织(包括癌旁乳腺组织17例和乳腺纤维腺瘤组织22例)中Syk、survivin和Ki-67的表达.结果 39例非癌组织中Syk均呈阳性表达,而survivin及Ki-67均呈阴性表达.52例乳腺癌组织中,Syk阳性22例(42.3%),survivin阳性36例(69.2%),Ki-67阳性32例(61.5%).乳腺癌中Syk阳性表达率低于非癌组织(χ2=31.01, P＜0.01);乳腺癌中survivin(χ2=41.82,P＜0.01)和Ki-67(χ2=34.37,P＜0.01)阳性表达率均高于非癌组织.相关分析显示,Syk与survivin的表达呈负相关(r=-0.53,P＜0.01);Syk与Ki-67的表达相关系数呈负值(r=-0.22,P=0.12);survivin与Ki-67的表达呈正相关(r=0.33,P＜0.05).结论 Syk可能有抑制乳腺癌细胞增殖和促进其凋亡的功能,提示Syk可能是一种抑癌基因,可作为乳腺癌新的分子标记物.联合检测Syk、survivin和Ki-67在乳腺癌中的表达,有望成为估价乳腺癌生物学行为的参考指标.     

乳腺浸润性导管癌中N-cadherin mRNA及蛋白的表达与预后分析

目的 探讨N-cadherin mRNA及蛋白在乳腺浸润性导管癌中的表达及其临床意义.方法 采用原位杂交技术和免疫组化SP法检测70例乳腺浸润性导管癌中N-cadherin mRNA及蛋白表达,以30例乳腺不典型导管增生为对照组.结果 乳腺浸润性导管癌中N-cadherin mRNA及蛋白阳性率分别为61.4%(43/70)、68.6%(48/70),乳腺不典型导管增生中N-cadherin mRNA及蛋白阳性率分别为3.3%(1/30)、6.7%(2/30),差异有统计学意义(P<0.01);N-cadherin mRNA及蛋白在乳腺浸润性导管癌中表达与淋巴结转移、TNM分期以及ER、PR表达有关,差异有统计学意义(P均<0.01);与患者年龄、肿瘤大小和组织学分级无关(P均>0.05);N-cadherin mRNA及蛋白在乳腺浸润性导管癌中表达呈正相关(rs=0.73,P<0.01);N-cadherin mRNA阳性患者生存率明显低于阴性患者,差异有统计学意义(P<0.01).结论 N-cadherin mRNA及蛋白在乳腺浸润性导管癌中的过表达提示其对乳腺癌发生、发展、浸润及转移起重要作用,并提示患者预后不良.     

间质细胞衍生因子1及其受体CXCR4在浸润性乳腺癌中的表达及其临床意义

目的 研究间质细胞衍生因子1(SDF-1)及其受体CXCR4在浸润性乳腺癌中的表达,并分析其与浸润性乳腺癌相关临床病理指标及淋巴结转移之间的关系.方法 采用免疫组织化学LSAB方法检测SDF-1/CXCR4在120例浸润性乳腺癌中的表达情况;采用地高辛标记的寡核苷酸探针进行原位杂交以检测趋化因子SDF-1在肿瘤环境中表达的部位及来源.结果 (1)SDF-1主要表达于肿瘤细胞的胞质和胞膜;SDF-1的胞质表达在淋巴结阳性组高于阴性组(P=0.033),且其表达程度与淋巴结受累数目、病理学分期、组织学分级、肿瘤大小及ER表达等指标呈正相关(P<0.05);(2)罕见SDF-1 mRNA表达的脉管内皮却可见SDF-1蛋白的表达,其表达程度与肿瘤胞质SDF-1着色正相关(P<0.01);且淋巴管内皮SDF-1的着色与淋巴结转移程度为正相关(P=0.005);血管内皮SDF-1的着色与肿瘤环境中的淋巴细胞浸润正相关(P<0.01),且同时伴有较多淋巴细胞浸润及SDF-1血管内皮着色阳性的病例,其淋巴结的转移程度分别高于仅有上述条件之一或二者均不具备的各组病例(P<0.05);(3)CXCR4也主要表达于肿瘤细胞的胞质和胞核;CXCR4的胞质表达在淋巴结阳性组高于阴性组(P<0.05),且其表达程度与淋巴结受累数目、病理学分期、组织学分级、肿瘤大小及HER2表达等呈正相关(P=0.005),而胞核的表达仅与PR的表达情况呈正相关(P<0.01);(4)瘤细胞质CXCR4与SDF-1的表达呈正相关(P=0.001).结论 浸润性乳腺癌肿瘤细胞SDF-1和CXCR4的表达与多项临床病理指标,尤其是淋巴结转移率及转移程度有关,可作为预测乳腺癌淋巴结转移及预后的免疫病理学指标,同时应注意肿瘤微环境中SDF-1的多个来源及定位的不同意义.     

乳腺癌患者原发磷酸化信号转导与转录激活因子3活性和白细胞介素-17表达的临床意义

目的 探讨炎性信号通路磷酸化信号转导和转录激活因子3（p-STAT）的原发活化状态及下游细胞因子白细胞介素（IL）-17表达在乳腺癌发生和发展中的作用及其对预后的影响。 方法 运用免疫组织化学Envision两步法检测了379例乳腺癌患者以及匹配癌旁245例乳腺腺病中IL-17表达和原发性p-STAT3的活化状态,分析了它们与乳腺癌组织学分型、TNM分期、临床分期及预后的相关性。统计学分析：计量数据使用t检验法,计数数据使用χ2 检验法。结果 1. IL-17在乳腺癌中的阳性表达率为95.8%,显著高于乳腺腺病中的阳性表达率85.3%（χ2=21.363,P<0.001）;具有活性的p-STAT3在乳腺癌中的阳性率为93.6%,也显著高于乳腺腺病中的阳性率62.0%（χ2=97.702,P<0.001）。2. IL-17和p-STAT3在乳腺癌 (包括乳腺浸润性导管癌、乳腺浸润性小叶癌和腺导管原位癌分型) 中的阳性率与乳腺癌组织学分型无相关性（χ2=1.245, P=0.535＞0.05）。3. IL-17和p-STAT3在乳腺癌中的强阳性率分别与淋巴结的转移成正相关（IL-17: χ2=7.806, P<0.01; p-STAT3: χ2=4.053, P<0.05）。4. 在乳腺癌组织中,IL-17表达与p-STAT3活性呈正相关（rs=0.136, P<0.01）。 结论 原发增高的p-STAT3活性及高表达的炎性细胞因子IL-17可能协同作用,产生炎性微环境,从而参与乳腺癌的发生和发展。     

乳腺癌P-gp与突变型P53表达关系及临床意义

目的探讨乳腺癌P-糖蛋白(P-gp)与突变型P53表达之间的关系及临床意义。方法应用免疫组织化学法检测36例乳腺癌患者癌组织及癌旁组织中P-gp和突变型P53蛋白表达。结果36例乳腺癌患者癌组织及癌旁组织中,P-gp阳性表达率分别为75.00%(27/36)和0.00%(0/36),两者差异有显著性(P<0.001);突变型P53阳性表达率分别为77.80%(28/36)和0.00%(0/36),两者差异有显著性(P<0.001)。P-gp和突变型P53在癌组织中共表达率66.67%(24/36),两者在癌组织中的表达呈正相关(rs=0.998,P<0.001)。结论P53基因突变与乳腺癌发生关系密切;在乳腺癌组织中,mdr1/P-gp与突变型P53蛋白表达之间存在强烈的相关性,mdr1基因可能在与P53突变有关的肿瘤发生期间被激活。     

肿瘤相关糖蛋白-72抗原在原发性乳腺癌组织中的表达及其临床意义

目的:探讨抗肿瘤相关糖蛋白(TAG-72)抗原的表达与原发性乳腺癌病理特征及预后的关系.方法:随机选取原发性乳腺癌患者118例, 应用SABC免疫组化方法检测TAG-72抗原的表达.并对其中的92例原发性乳腺癌患者中作术后为期5年的随访, 分析TAG-72抗原与原发性乳腺癌患者预后的相关性.结果:TAG-72抗原在原发性乳腺癌组织中的阳性表达率为78.81% (93/118), 并与原发性乳腺癌组织的临床病理学特征及患者的预后均有密切的关系.在直径较大(P<0.05)、 TNM分期较高(P<0.05)、淋巴结转移(P<0.01)及组织学分级低(P<0.01)的肿瘤组织中, TAG-72抗原高表达.此外, TAG-72抗原阳性表达的原发性乳腺癌患者的生存率明显低于阴性表达的患者 (P<0.01).结论:TAG-72抗原的表达可能与原发性乳腺癌的发生、浸润、转移有关;TAG-72抗原可以作为一个肿瘤标志物在临床中应用, 检测其在原发性乳腺癌组织中的阳性表达率, 并结合临床病理学分级, 可提高对患者预后判断的准确性.     

浸润性乳腺癌中基质金属蛋白酶-13蛋白的表达及其与其他相关因子和预后的关系

目的 探讨浸润性乳腺癌中基质金属蛋白酶(MMP)-13蛋白在肿瘤细胞和间质细胞中的表达及其与肿瘤临床病理、生物学指标以及预后的相关性.方法 采用组织芯片免疫组织化学染色sP法检测263例浸润性乳腺癌组织中MMP-13、ER、PR、HER2、MMP-2、MMP-9、基质金属蛋白酶组织抑制因子(TIMP)-1、TIMP-2蛋白的表达及表达间的相关性.结果 MMP-13在肿瘤细胞及间质纤维母细胞中均表达,肿瘤细胞中MMP-13过表达与淋巴结受累和高组织学分级相关(均P<0.01),且与HER2表达(P=0.015)和肿瘤细胞TIMP-1蛋白表达相关(P<0.01).MMP-13过表达与患者总生存期缩短相关,分层分析显示MMP-13的过表达分别与淋巴结阳性患者总生存期和HER2阳性和阴性表达状态下的患者总生存期有关.间质纤维母细胞表达MMP-13尽管与肿瘤细胞表达者有相关性,且与淋巴结状态和HER2表达也相关,但评估预后的价值较弱.经单因素分析,肿瘤直径、组织学分级、淋巴结和PR、HER2表达状态及肿瘤表达的TIMP-1和MMP-13均是有意义的预后指标;但多因素分析显示仅肿瘤直径、组织学分级、淋巴结状态、HER2表达、肿瘤中TIMP-1和MMP-13表达是独立预后因素.结论 MMP-13蛋白与浸润性乳腺癌的侵袭和转移相关,有可能作为预后不良的指标.     

FOXP3在乳腺癌中的表达及临床意义

目的 研究FOXP3+淋巴细胞和FOXP3蛋白在人乳腺癌细胞中的表达及其与患者临床病理特征的关系.方法 采用组织芯片平台,应用免疫组织化学方法 检测92例浸润性乳腺癌和26例癌旁乳腺组织中FOXP3+淋巴细胞和FOXP3蛋白的表达.结果 乳腺癌间质浸润的FOXP3+淋巴细胞阳性率高于癌旁组织(32.7% vs 7.7%,P<0.01);乳腺癌实质FOXP3蛋白阳性率也高于癌旁组织(52.2% vs 7.7%,P<0.01);乳腺癌间质浸润的FOXP3+淋巴细胞数和癌实质FOXP3蛋白表达无相关性(P>0.05);乳腺癌间质浸润的FOXP3+淋巴细胞与淋巴结转移、组织学分级、pTNM分期和c-erbB-2过表达呈正相关;乳腺癌实质FOXP3蛋白表达与淋巴结转移呈正相关(P<0.05);乳腺癌间质浸润的FOXP3+淋巴细胞和乳腺癌实质FOXP3蛋白表达与乳腺癌的预后无关(P>0.05).结论 FOXP3+淋巴细胞可能在乳腺癌的免疫逃逸中发挥一定作用;FOXP3表达异常可能与乳腺癌的转移关系密切;FOXP3可作为评估乳腺癌生物学行为的一种潜在标记物.     

Tumour angiogenesis and c-Met pathway activation – implications in breast cancer

Breast cancer is a heterogeneous disease with wide range of clinical behaviour. Tumour angiogenesis and metastasis have been considered as prognostic markers of the breast carcinoma, and c-Met, a transmembrane receptor tyrosine kinase has been implicated in both these processes of tumour progression. This study was conducted to elucidate c-Met and downstream signalling pathways in breast cancer and correlate with angiogenesis as assessed by microvessel density (MVD) and other prognostic parameters including lymph node metastases. Microvessel density (MVD) was assessed by endothelial cell (CD34) marker in breast cancers. c-Met was evaluated by immunohistochemistry for protein expression and by copy number assay for amplification at gene level. PCR array for gene expression related to c-Met, RAS-MAPK, PI3K-AKT and angiogenesis pathway was performed by real-time PCR. c-Met protein, copy number and mRNA expression did not differ significantly with the lymph node status or MVD. However, Her-2 overexpressing group showed c-Met protein overexpression and amplification. c-Met protein overexpression was also noted in the Luminal B subtype though no amplification was noted. Thus, the c-Met immunohistochemistry score and the c-MET copy numbers did not correlate with each other. c-Met downstream pathway genes (RAS-MAPK, PI3K-AKT and angiogenesis pathway) showed significant upregulation in Luminal B molecular subtype, lymph node-positive cases and cases with high MVD. The downstream signalling pathways (angiogenesis, RAS-MAPK and PI3K-AKT) were associated high MVD, lymph node metastases, and Her-2 and Luminal B subtype. Since inhibitors of these pathways are commercially available, these can be of therapeutic significance.     

Differential expression of c-Met, its ligand HGF/SF and HER2/neu in DCIS and adjacent normal breast tissue

AIMS: Tyrosine kinase receptors Her2/neu and c-Met play an important role in breast cancer development and progression. Our aim was to determine the expression of c-Met, its ligand hepatocyte growth factor/scatter factor (HGF/SF) and Her2/neu in ductal carcinoma in situ (DCIS) lesions of the breast (n = 39) by two different immunocytochemical techniques, classical immunohistochemistry and immunofluorescence, and to correlate their expression levels with histopathological and clinical characteristics. METHODS AND RESULTS: Both methods revealed similar c-Met staining patterns in both the in situ component and the adjacent normal tissue (P < 0.001). However, an imbalance in c-Met expression between tumour and surrounding normal tissue was correlated with high-grade DCIS (Van Nuys Grade 3). No correlation existed between Her2/neu and c-Met expression. High HGF/SF immunoreactivity was observed in 43.6% of the cases, yet the adjacent cellular stroma revealed only low levels of HGF/SF. No correlation existed between c-Met, Her2/neu or HGF/SF expression and clinicopathological factors. CONCLUSION: An imbalance in c-Met expression between tumour and surrounding normal tissue is associated with an aggressive DCIS phenotype. Moreover, c-Met and HGF/SF may contribute to tumour development by different means than those controlled by Her2/neu.     

c-Met对三阴性乳腺癌细胞增殖及阿霉素耐药性的影响

目的:研究c-Met对三阴性乳腺癌细胞株MDA-MB-231活力及对阿霉素耐药性的影响。方法:构建阿霉素耐药的MDA-MB-231/ADR细胞系,实时荧光定量PCR及Western blotting技术检测不同细胞系中c-Met mRNA及蛋白的表达。脂质体转染c-Met-siRNA及表达质粒或AKT-siRNA,Western blotting检测转染效率;四甲基偶氮唑法(MTT法)检测细胞的活力及对阿霉素的敏感性。结果:对阿霉素耐药的MDA-MB-231/ADR细胞中cMet的mRNA及蛋白表达均显著高于对照的MDA-MB-231细胞,转染高表达c-Met的质粒可增加MDA-MB-231细胞的活力并降低其对阿霉素的敏感性,而利用siRNA抑制耐药细胞株中c-Met的表达后,可以逆转MDA-MB-231/ADR细胞对阿霉素的耐药。此外,c-Met可以磷酸化激活细胞中的AKT,并通过该信号分子增加MDA-MB-231细胞活力并诱导耐药。结论:c-Met可作为一个重要的靶点应用于三阴性乳腺癌的治疗。     

Expression of the hepatocyte growth factor/c-Met pathway is increased at the cancer front in breast carcinoma

Expression of hepatocyte growth factor (HGF) and c-Met (HGF receptor) has been reported in many neoplasms. We investigated coexpression of HGF and c-Met to determine the role of the HGF/c-Met pathway in breast carcinoma, especially at the cancer front. Eighty-eight cases of carcinoma of the breast were studied by immunohistochemistry and by in situ hybridization for HGF and c-Met expression. The staining pattern was termed "front accentuation pattern" when it was most conspicuous at the cancer front. HGF and c-Met proteins were expressed in cancer and stromal cells, with autocrine and paracrine patterns. The front accentuation pattern of c-Met was observed in cancer cells, but not in stromal cells. The front accentuation pattern was not observed in HGF. Coexpression of HGF and c-Met at the cancer front was correlated with histologic grade, reduced patient survival and a high Ki-67 labeling index. Our findings suggest that the HGF/c-Met pathway acts primarily as a mitogen, especially at the cancer front, in a paracrine manner and affects some clinical factors, including patient survival.     

Notch1受体在乳腺癌组织中的表达及其与临床病理特征的关系

目的 探讨Notch1受体与乳腺癌患者的临床病理特征及预后的关系.方法 应用免疫组化技术检测106例乳腺癌组织中Notch1受体、ER、PR、CerbB-2受体表达情况,分析其与临床病理特征及预后的相关性.结果 乳腺癌组织中Notch1受体表达明显高于癌旁正常组织(P＜0.05);Notch1受体表达与CerbB-2具有相关性(P＜0.05),与ER、PR无显著相关性(P＞0.05);Notch1受体高表达组5年生存率低于低表达组(P＜0.05).结论 乳腺癌组织中Notch1受体表达明显高于癌旁正常组织;Notch1受体表达与CerbB-2具有相关性,推测Notch1受体可能与CerbB-2存在交互作用;Notch1受体高表达与预后不良有关.     

Expression of c-Met and heparan-sulfate proteoglycan forms of CD44 in colorectal cancer

In colorectal cancer patients, prognosis is not determined by the primary tumor but by the formation of distant metastases. Molecules that have been implicated in the metastatic process are the proto-oncogene product c-Met and CD44 glycoproteins. Recently, we obtained evidence for functional collaboration between these two molecules: CD44 isoforms decorated with heparan sulfate chains (CD44-HS) can bind the c-Met ligand, the growth and motility factor hepatocyte growth factor/scatter factor (HGF/SF). This interaction strongly promotes signaling through the receptor tyrosine kinase c-Met. In the present study, we explored the expression of CD44-HS, c-Met, and HGF/SF in the normal human colon mucosa, and in colorectal adenomas and carcinomas, as well as their interaction in colorectal cancer cell lines. Compared to the normal colon, CD44v3 isoforms, which contain a site for HS attachment, and c-Met, were both overexpressed on the neoplastic epithelium of colorectal adenomas and on most carcinomas. Likewise, HGF/SF was expressed at increased levels in tumor tissue. On all tested colorectal cancer cell lines CD44v3 and c-Met were co-expressed. As was shown by immunoprecipitation and Western blotting, CD44 on these cells lines was decorated with HS. Interaction with HS moieties on colorectal carcinoma (HT29) cells promoted HGF/SF-induced activation of c-Met and of the Ras-MAP kinase pathway. Interestingly, survival analysis showed that CD44-HS expression predicts unfavorable prognosis in patients with invasive colorectal carcinomas. Taken together, our findings indicate that CD44-HS, c-Met, and HGF/SF are simultaneously overexpressed in colorectal cancer and that HS moieties promote c-Met signaling in colon carcinoma cells. These observations suggest that collaboration between CD44-HS and the c-Met signaling pathway may play an important role in colorectal tumorigenesis.     

腺病毒载体介导的RNAi对SK-BR-3细胞c-Met表达的影响

目的:通过腺病毒载体介导的RNA干扰技术抑制乳腺癌细胞HGF受体c-Met的表达,抑制乳腺癌细胞增殖、诱导细胞凋亡。方法:PCR法获得人U6启动子及带有c-Met反向互补靶序列的片段HU6shmet;利用腺病毒载体将其传递至SK-BR-3细胞;RNA狭缝杂交检测SK-BR-3细胞c-Met mRNA水平,Western印迹检测c-Met蛋白水平。结果:获得了带有人U6启动子及c-Met反向互补靶序列的重组腺病毒载体rAdUshmet1和rAdUshmet2。转导了重组腺病毒的SK-BR-3细胞的c-Met mRNA和蛋白相对表达量均有所下降。结论:腺病毒载体rAdUshmet通过抑制HGF受体c-Met表达,能在一定程度上阻断HGF-c-Met信号转导通路,有可能成为对乳腺癌进行基因治疗的有效载体。     

Clinical and functional significance of loss of caveolin-1 expression in breast cancer-associated fibroblasts

Loss of caveolin-1 (Cav-1) expression in breast cancer-associated fibroblasts (CAFs) is predictive of poor prognosis in breast cancer, but its function has not been established. Our study tested the hypotheses that loss of Cav-1 expression in breast fibroblasts was associated with poor prognosis in breast cancer, through promotion of breast cancer cell invasion. Cav-1 stromal expression was immunohistochemically assessed in 358 breast cancers. Cav-1 expression in primary breast fibroblasts was analysed by western blot. Modified Boyden chamber assays determined fibroblast ability to promote invasion of breast cancer cells. The impact of siRNA silencing of Cav-1 in fibroblasts was evaluated using invasion assays and 3D co-culture assays. Loss of Cav-1 expression in breast stroma was significantly associated with decreased breast cancer-specific and disease-free survival (p = 0.01). Mean survival was 72 months (Cav-1(+) group) versus 29.5 months (Cav-1(-) group). This was confirmed in multivariate analysis. Cav-1 expression was significantly decreased in CAFs compared to normal fibroblasts (p = 0.01) and was associated with increased invasion-promoting capacity. Cav-1 siRNA-treated fibroblasts promoted significantly increased invasion of MDA-MB-468 and T47D breast cancer cells from 27% (control) to 67% (p = 0.006) and from 37% to 56%, respectively (p = 0.01). 3D co-cultures of MDA-MB-468 cells with myoepithelial cells led to the formation of organized cohesive structures when cultured with conditioned media from fibroblasts but resulted in a disorganized appearance in the presence of conditioned media from Cav-1 siRNA-treated fibroblasts, accompanied by loss of E-cadherin expression in tumour cells. Our data confirm that loss of stromal Cav-1 in breast cancer predicts poor outcome. At a functional level, Cav-1-deficient CAFs are capable of significantly increasing the invasive capacity of breast cancer cells.     

乳腺癌中p27和c-erbB-2的表达及意义

目的　探讨乳腺癌中 p2 7和c erbB 2表达情况和意义。 方法　用免疫组化S P法检测 4 0例乳腺癌中 p2 7和c erbB 2的表达。结果　正常乳腺组织c erbB 2表达阴性 ,癌组织中阳性率为 37 5 % (15 / 4 0 ) ,两者差异有显著性 (P <0 0 0 1)。 4 0例乳腺癌组织中 p2 7高表达率为 32 5 % (13/ 4 0 ) ,正常乳腺组织高表达为 80 % ,两者差异有显著性 (P <0 0 0 1)。p2 7高表达与癌组织分化、淋巴结转移和复发有关 (P <0 0 5 )。结论　基因p2 7和c erbB 2表达异常是乳腺癌产生的机制之一 ,与乳腺癌的发生及发展有关。p2 7可能是乳腺癌的一个重要预后指标     

ACTL8的表达与乳腺癌临床病理特征及预后的关系

目的:探讨肌动蛋白样蛋白8(ACTL8)在乳腺癌中的表达及其与乳腺癌临床病理特征及预后的关系。方法:采用Western blot方法检测人正常乳腺上皮细胞株MCF-10A和5种乳腺癌细胞株中ACTL8蛋白的表达;采用免疫组织化学方法检测6例乳腺癌标本及其对应的癌旁组织中ACTL8蛋白的表达;收集TCGA乳腺癌数据集,将488例乳腺标本纳入,分析ACTL8的mRNA表达水平与乳腺癌患者临床病理特征及预后的关系。结果:ACTL8蛋白在乳腺癌细胞株T47D、BT474、HCC1954和SKBR3中表达显著高于乳腺上皮细胞株MCF-10A;ACTL8蛋白在乳腺癌组织中的表达也显著高于癌旁组织;ACTL8 mRNA表达与乳腺癌患者年龄、肿瘤大小、临床TNM分期和淋巴结转移相关(P0.05)。ACTL8 mRNA高表达的乳腺癌患者5年内生存率低、预后差。结论:ACTL8在乳腺癌组织中高表达并与乳腺癌临床病理特征及预后密切相关,提示ACTL8可作为判断乳腺癌预后的标志物。