乳腺浸润性导管癌连接蛋白43和上皮性钙黏蛋白相关性研究

目的探讨乳腺浸润性导管癌组织中间隙连接蛋白43(Cx43)及上皮性钙黏蛋白(E-cad)表达中的相关性。方法采用Elivision免疫组织化学法对89例乳腺侵润性导管癌组织及48例分区组织的Cx43与E-cad检测。结果乳腺浸润性导管癌的肿瘤区、交界区和远癌区的Cx43和E-cad蛋白表达具有较好的一致性(γ=0.460,P0.01);在肿瘤区两者同时为阴性表达时,淋巴结转移率最高。结论 Cx43和E-cad在乳腺浸润性导管癌发生和发展过程中具有一定的协同作用,与其发生浸润转移有关。     

乳腺浸润性癌PS2蛋白的表达及其与预后的关系

目的探讨ＰＳ２蛋白在乳腺浸润性癌中的表达及其与预后的关系。方法应用ＬＳＡＢ免疫组化法检测ＰＳ２蛋白在８６例乳腺浸润性癌中的表达。结果ＰＳ２蛋白的表达率为６６．２７％（５７／８６）。在下列一些情况中，ＰＳ２蛋白的表达率有区别：（１）８６例中，５年以上组８０．５５％（２９／３６），５年以下组５６．００％（２８／５０），差异有显著性意义（Ｐ＜０．０２５）；（２）未停经组６２例，５年以上组８６．２０（２５／２９），５年以下组５４．５４％（１８／３３），差异有显著性意义（Ｐ＜０．００５），已停经组２４例，５年以上组４／７例，５年以下组５８．８０％（１０／１７），差异无显著性意义；（３）腋窝淋巴结转移６２例，５年以上组８２．３５％（１４／１７），５年以下组５５．５５％（２５／４５），差异有显著性意义（Ｐ＜０．０５）；腋窝淋巴结阴性２４例，５年以上组７８．９４％（１５／１９），５年以内组３／５例，差异无显著性意义。结论本研究表明，ＰＳ２蛋白的阳性表达与５年生存期正相关，ＰＳ２阳性的表达可以作为乳腺癌的一项预后指标；ＰＳ２蛋白表达对未停经患者的内分泌治疗具有一定的指导意义；腋窝淋巴结阳性患者ＰＳ２蛋白表达与较好的预后相关。     

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.     

上皮钙依赖粘附素相关分子在乳腺浸润性小叶癌和导管癌中的表达及意义

目的 探讨上皮钙依赖粘附素相关分子α-、β-、γ-catenin在乳腺浸润性小叶癌（ILC）和浸润性导管癌（IDC）中的表达及其意义。方法 采用免疫组织化学LSAB法检测了19例ILC和32例IDC组织中α-、β-、γ-catenin的表达,并根据阳性癌细胞占肿瘤细胞的比例进行半定量化分析和统计学x^2检验。结果 α-、β-、γ-catenin在19例ILC中表达缺失和明显减少的分别为15例（78.9%),10例（52.6%)和16例（84.2%),而在32例IDC癌组织中的表达缺失和明显减少为24例（75.0%),14例（43.8%)和26例(81.3%)例。另外,这3种蛋白在浸润性癌组织中表达强度弱于原位癌灶的表达强度。α-catenin和β-catenin在乳腺浸润性癌中的表达具有明显的正相关性,未发现α-、β-、γ-catenin在乳腺浸润性癌中的表达与有无伴有淋巴结转移病例之间的关系有统计学意义。结论 α-、β-、γ-catenin在乳腺ILC和IDC中表达均为明显缺失和减少,说明这些粘附分子在乳腺浸润性癌发生中确实丧失了其正常的细胞粘附功能。     

乳腺浸润性微乳头状癌上皮性钙黏附素的表达及意义

目的 研究细胞黏附分子,在乳腺浸润性微乳头状癌肿瘤细胞的集团性浸润、转移中的表达和作用。方法 复习2002年1月～2003年5月所有手术切除乳腺癌组织切片,按WHO乳腺癌分类分组,浸润性微乳头状癌(IMPC)64例、浸润性导管癌(IDC)57例。采用免疫组织化学标记的链霉素抗生物素蛋白-生物素(LSAB)法检测64例IMPC中E-钙黏附素的表达,并同IDC加以比较。结果 E-钙黏附素主要表达于IMPC细胞膜;IMPCE-钙黏附素表达率(85．9％,55／64)明显高于IDC(43．9％,25／57),并且在微乳头状肿瘤细胞集团内的细胞间连接面表达正常,而在细胞集团面向间质侧的表达明显减弱或不表达;IMPC组的淋巴结转移率(85．9％,55／64)明显高于IDC(52．6％,30／57)．．其淋巴结阳性、E-钙黏附素阳性病例的d-连接素、B-连接素共同表达率(45．1％,26／51)也明显高于IDC(15．4％,2／13)。结论 IMPC的微乳头状肿瘤细胞集团内细胞间黏附性强、而与间质间的黏附性减弱或消失的特性可能是IMPC具有高转移潜能的原因之一。     

SLP-2基因在喉鳞状细胞癌和乳腺浸润性癌组织中的表达及其与预后的关系

目的 探讨两种恶性上皮性肿瘤组织--喉鳞状细胞癌(简称喉癌)和乳腺浸润性癌(简称乳腺癌)中stomatin like protein-2(SLP-2)基因在mRNA和蛋白水平的表达,及其与肿瘤的临床病理参数和预后的相关性.方法 应用逆转录聚合酶链反应(RT-PCR)检测了46对喉癌及喉正常上皮组织中SLP-2基因的表达,Western blot方法检测了其中10对标本的SLP-2蛋白表达,同时采用免疫组织化学方法分别检测了104例喉癌组织芯片和263例乳腺癌组织芯片中SLP-2蛋白的表达水平,分析SLP-2蛋白的表达与临床病理变量之间的关系.结果 RT-PCR结果显示SLP-2基因在46例喉癌中的38例肿瘤组织中的表达升高(83%,38/46),喉正常上皮组织中表达阴性.Western blot结果显示,有7例喉癌组织中SLP-2蛋白表达显著高于对应的喉正常上皮组织.喉癌组织芯片的免疫组织化学染色结果显示,与全部20例喉正常上皮组织的阴性表达(0/20)相比,SLP-2蛋白染色在104例喉癌组织中有36例出现了过表达(34.6%,36/104;P=0.000).与喉正常上皮表达相比,喉癌组织中SLP-2基因在mRNA和蛋白水平的表达均明显升高.SLP-2蛋白过表达与喉癌患者的临床分期较晚(P<0.01)和淋巴结发生转移(P=0.003)密切相关.乳腺癌组织芯片免疫组织化学染色结果显示,与在正常乳腺组织中的阴性表达(0/10)相比,SLP-2蛋白在乳腺癌组织中呈现过表达(52.5%,138/263),差异有统计学意义(P:0.000),且该蛋白的过表达与乳腺肿物的大小(P=0.020)、淋巴结转移(P<0.01)、临床分期Ⅲ期(P<0.01)以及发生远处转移(P=0.002)密切相关.此外,还与HER2/neu蛋白的表达存在显著相关性(P:0.037),生存分析表明,SLP-2蛋白过表达乳腺癌患者总生存率显著降低.多因素分析显示淋巴结状态、HER2/neu蛋白表达和SLP-2蛋白表达可能作为独立的预后因子.结论 SLP-2蛋白的过表达可能与喉癌和乳腺癌的侵袭、转移过程密切相关,并可能作为独立的预后指标提示乳腺癌患者预后不良.     

上皮性卵巢癌中PARP-1的表达及其与EMT的关系

 目的: 探讨上皮性卵巢癌(epithelial ovarian cancer,EOC)中聚腺苷二磷酸核糖聚合酶-1[poly(ADP-ribose) polymerase-1,PARP-1]的表达及其与上皮-间质转化(epithelial-mesenchymal transition,EMT)的关系。方法: 免疫组化、实时荧光定量PCR法检测EOC和良性卵巢肿瘤组织中PARP-1、E-钙黏蛋白(E-cadherin)、波形蛋白(vimentin)和转录调控因子Snail的表达;Western blotting法检测高效PARP-1抑制剂PJ34处理SKOV3细胞后PARP-1、E-cadherin、vimentin和Snail蛋白的表达。结果: PARP-1、vimentin和Snail在EOC中阳性表达率高于良性卵巢肿瘤组织,而E-cadherin则相反,差异均有统计学显著性(P<0.05)。PARP-1、E-cadherin、vimentin和Snail与EOC的病理分级、临床分期和有无淋巴结转移有关(P<0.05),与年龄和病理类型无关。E-cadherin表达与PARP-1表达呈负相关(P<0.05),vimentin、Snail表达与PARP-1表达呈正相关(P<0.05)。EOC中PARP-1、vimentin和Snail mRNA的相对表达量高于良性卵巢肿瘤组织,E-cadherin mRNA的相对表达量低于良性卵巢肿瘤组织,差异均具有统计学显著性(P<0.05)。PJ34处理SKOV3细胞后,PARP-1、vimentin和Snail的蛋白水平明显下降,E-cadherin的蛋白水平显著提高,差异有统计学显著性(P<0.05)。结论: PARP-1通过调控E-cadherin、vimentin和Snail的表达促进EOC上皮间质转化。PARP-1及其参与的上皮-间质转化在EOC进展中发挥重要作用。     

乳腺癌中乙醛脱氢酶1与上皮性钙黏蛋白、神经性钙黏蛋白关系的研究

乳腺癌干细胞是一类具有自我更新及多向分化潜能的原始细胞,在一定条件下可以分化成多种不同功能的细胞,从而影响乳腺癌的发生、发展、转移、耐药及复发等生物学行为[1]。上皮-间质转化(epithelial-mesenchymal transition,EMT)在乳腺癌浸润转移过程中起着重要作用。本实验应用免疫组织化学方法研究乳腺癌干细胞标志物乙醛脱氢酶1(ALDH1)蛋白与EMT标志蛋白上皮性钙黏蛋白     

淋巴结转移密度与乳腺浸润性导管癌预后的关系

目的探讨淋巴结转移密度与手术治疗乳腺浸润性导管癌患者预后的关系。方法回顾性分析113例乳腺浸润性导管癌的临床资料,按淋巴结转移密度分为ND40组、ND=0组和ND≤40组,采用Kaplan-Meier法和Cox比例风险模型,比较临床病理特征及淋巴结转移密度评价手术治疗乳腺浸润性导管癌患者5年无瘤生存率和总生存率的价值。结果 ND40组、ND=0组和ND≤40组5年无瘤生存率及总生存率,差异有统计学意义(P均0.05)。在Ⅲ期乳腺癌患者中,淋巴结转移密度提供良好的分层意义,ND40组Ⅲ期乳腺癌与Ⅳ期乳腺癌预后无差异(P=0.453)。单因素分析显示,脉管癌栓、淋巴结转移密度、TNM分期、雌、孕激素受体状态及p N分期均与患者的5年无瘤生存率和总生存率有关(P均0.05)。多因素分析显示,组织学分级及淋巴结转移密度是影响患者5年无瘤生存率的独立因素(P均0.05);淋巴结转移密度是影响患者5年总生存率的独立因素(P0.05)。结论淋巴结转移密度是手术治疗乳腺浸润性导管癌患者预后的独立因素,提示其可作为乳腺癌预后的参考标准,ND40组提示预后不良。     

转录因子Snail及黏附分子E-cadherin在胃癌中的表达及意义

目的探讨转录因子Snail及黏附分子E—cadherin在胃癌中的表达及意义。方法采用免疫组化sP法检测96例胃癌组织和80例癌旁组织中Snail、E—cadherin的表达,分析两者在不同组织类型与分化程度胃癌中的表达,以及与临床病理因素之间的关系。结果胃癌组织E—cadherin的阳性率（37．5％）显著低于癌旁组织（100％）（P〈0．05）,E—cadherin的表达与胃癌不同分化程度、组织学类型、浸润深度、淋巴结转移、临床分期及远处转移有关（P〈0．05）。胃癌组织Snail阳性率（83．3％）显著高于癌旁组织（41．25％）（P〈0．05）,Snail的表达与胃癌不同分化程度、组织学类型、浸润深度、淋巴结转移及远处转移有关（P〈0．05）。胃癌组织中E—cadherin与Snail的表达呈负相关（P〈0．05）。结论E—cadherin蛋白低表达与Snail蛋白高表达可能是胃黏膜恶性转变以及胃癌发生浸润转移的重要生物学标志。联合检测E—cadherin及Snail对预测胃癌浸润转移有重要意义。     

Biological and prognostic significance of stratified epithelial cytokeratins in infiltrating ductal breast carcinomas

 The biological significance of the differential expression of cytokeratin (CK) polypeptides in breast carcinomas is unclear. We examined the CK profiles of 101 primary infiltrating ductal breast carcinomas using monoclonal antibodies directed against 11 different CKs and against vimentin. Two major CK phenotypes were distinguished: first, a phenotype expressing only the simple-epithelial CKs 7 (variably), 8, 18 and 19, and secondly, a bimodal phenotype co-expressing significant amounts of one or more of the stratified-epithelial CKs 4, 14 and 17. The vast majority of G1 and G2 carcinomas had the simple-epithelium phenotype, as did a subgroup of G3 carcinomas. Interestingly, the majority (62%) of G3 carcinomas exhibited the bimodal phenotype, with the expression of CKs 4, 14 and 17 being statistically correlated with poor histological differentiation and absence of steroid hormone receptors. The distribution of vimentin only partially overlapped with that of these stratified-epithelial CKs. Prognostic analyses suggested that the presence of CKs 4, 14 and/or 17 was associated with short overall and disease-free survival in subgroups comprising G3, oestrogen-receptor-negative and vimentin-negative tumours. In node-positive tumours the correlation between these CKs and a shorter disease-free interval attained statistical significance (log rank, 0.0096). Thus, abnormal CK profiles in ductal breast carcinomas appear to reflect disturbed regulation of differentiation-related gene expression programmes and may prove to be of clinical value. Received: 26 August 1997 / Accepted: 11 February 1998     

Clinical significance of NOB1 expression in breast infiltrating ductal carcinoma

Background: NIN/RPN Binding protein 1 homologue (NOBp1), encoded by NOB1 gene, was reported to play an essential role in the oncogenesis and prognosis of carcinomas. We conducted a study to reveal its expression and clinical significance in breast infiltrating ductal carcinoma. Methods: To explore the relationship between NOB1 expression and the clinical TNM (cTNM), 162 patients who undergone surgery were involved in the study. Compared to healthy tissues, abnormal localization and higher level of NOB1 in tumor cells was observed by Immunohistochemistry staining. Real-time PCR and western-blotting verified the up-regulation of NOB1 in carcinoma individuals. Results: A significant correlation between high level of NOB1 and the T stage, lymph node metastasis and cTNM was shown. Furthermore, patients with higher level of NOB1 predicted a declined overall survival (OS). Notably, multivariate analyses by Cox’s proportional hazard model revealed that expression of NOB1 was an independent prognostic factor in breast infiltrating ductal carcinoma. Conclusions: In summary, our present study clarify that the aberrant expression of NOB1 in breast infiltrating ductal carcinoma is possibly involved with tumorigenesis and development, and the NOB1 protein could act as a potential biomarker for prognosis assessment of breast infiltrating ductal carcinoma. Related mechanism is worthy of further investigation.     

胃腺癌中p53、E-cadherin的表达及其预后因素分析

目的 研究胃腺癌组织中p53、E-cadherin的表达,分析它们和临床病理参数对预后的影响.方法 采用组织芯片和免疫组化检测150例胃腺癌中p53、E-cadherin的表达,分析它们和临床病理参数对预后的影响.单因素分析用Kaplan-Meier法计算累积生存率并比较患者术后平均生存时间,多因素分析用COX回归.结果 150例胃腺癌中p53阳性率为31.3%;E-cadherin阳性率为91.3%.随访到的74例胃腺癌患者1年生存率为83.8%,3年生存率为70.3%,5年生存率为63.5%.单因素分析年龄、分化程度、Laurén分类、浸润深度、淋巴结状况、pTNM分期是影响胃腺癌预后的因素;多因素分析p53、年龄、淋巴结状况为影响胃腺癌预后的独立因素(P<0.05).结论 p53、年龄、分化程度、Laurén分类、浸润深度、淋巴结状况和pTNM分期是影响胃腺癌预后的因素,而E-cadherin和组织学分类不是影响胃腺癌预后的因素.     

The biological and prognostic significance of cell polarity and E-cadherin in grade I infiltrating ductal carcinoma of the breast

Grading of breast cancer based on the modified Scarff, Bloom, and Richardson system provides invaluable prognostic information. Recent evidence suggests that most tumours do not usually progress between grades and that groups of tumours within each grade are biologically distinct. This study has explored one potential aspect of biological tumour heterogeneity within grade by examining the relationship between cell polarity, the cell adhesion molecule E-cadherin, a major effector of cell polarity, and outcome, in 149 grade I infiltrating ductal breast carcinomas. Polarity was evaluated by studying the degree to which three features of polarized epithelial cells—nuclear ordering, basal positioning of nuclei within cells, and apical snouting/blebbing—were present in these tumours. E-cadherin expression was investigated using the antibody HECD-1. A low degree of tubule formation was correlated with poor nuclear ordering ( p< 0·01). The three histological features—nuclear ordering, basal nuclei, and apical blebbing—were all correlated with each other (all p< 0·0001). Polarity measurements did not correlate with survival. E-cadherin expression did not correlate with polarity and negative tumours were still able to form tubules. Surprisingly, strong E-cadherin immunostaining correlated with poor survival, tumour size, and nodal status. On univariate parametric (Weibull) survival models, high E-cadherin scores and tumour size were both significant predictors of survival in this group. Copyright © 1999 John Wiley & Sons, Ltd.     

Clinicopathologic significance of the expression of Snail in hepatocellular carcinoma

Background/Aims

E-cadherin is involved in intercellular binding and cellular polarity formation. Snail is a key regulator of the epithelial-mesenchymal transition and is closely associated with tumor invasiveness due to its ability to suppress E-cadherin expression. We investigated the expressions of E-cadherin and Snail in hepatocellular carcinoma (HCC) tissue to determine the clinical significance of these proteins in HCC.

Methods

Immunohistochemistry was used to examine the expressions of E-cadherin and Snail in resected tissues from 59 patients diagnosed with HCC. We also evaluated the relationship between the expressions of these two molecules in HCC tissue and clinicopathologic factors in the patients.

Results

Immunohistochemistry showed that Snail was stained in 20.3% of the HCC tissues and 3.4% of noncancerous tissues. Snail was not stained in the area of E-cadherin expression. The expression of Snail in the HCC tissue was associated with poorly differentiated HCC (P=0.028). The expression of Snail without E-cadherin staining in HCC tissue was significantly associated with postoperative HCC recurrence (P=0.013).

Conclusions

The expression of Snail in HCC tissue was associated with decreased expression of E-cadherin and poorly differentiated HCC. The expression of Snail without E-cadherin staining in HCC was associated with postoperative recurrence.