E-cadherin、β-catenin及p120在上皮性卵巢癌中的表达及临床病理意义

目的:探讨黏附复合体相关蛋白E-cadherin、β-catenin及p120在人类卵巢癌组织中的表达及其与患者临床病理特征及预后的关系.方法:采用免疫组织化学染色法检测281例卵巢癌患者肿瘤组织中E-cadherin、β-catenin及p120的表达水平,分析其与临床病理特征之间的关系,比较其在卵巢癌原发灶与转移灶之间的差异.结合患者随访资料,利用Kaplan-Meier法绘制生存曲线,Log-rank法分析E-cadherin、β-catenin或p120的表达水平与卵巢癌患者预后的关系,COX回归模型分析卵巢癌患者预后的独立预测因素.结果:β-catenin在卵巢癌原发灶与转移灶间表达水平具有统计学差异(P=0.018),卵巢癌组织中p120的表达水平与患者FIGO分期(P=0.043)、组织学类型(P＜0.001)、肿瘤分级(P ＜0.001)有关,Spearman法分析证实E-cadherin与β-catenin(P=0.005)、β-catenin与p120(P ＜0.001)、E-cadherin与p120(P ＜0.001)具有相关性,卵巢癌组织中β-catenin(P=0.008)及p120(P =0.006)低表达的患者较高表达者总生存期缩短,多因素分析发现FIGO分期、β-catenin或p120表达水平是卵巢癌患者总生存期的独立预测因素.结论:鉴于黏附复合体在卵巢癌发生、浸润及转移中均发挥了重要作用,综合评估其相关蛋白E-cadherin、β-catenin及p120的表达水平,有助于判断卵巢癌的生物学行为及预测患者的预后.     

乳腺浸润性导管癌和浸润性小叶癌细胞粘附分子与雌、孕激素受体表达及意义

目的：探讨乳腺浸润性导管癌（invasive ductal carcinoma,IDC)和浸润性小叶癌（invasive lobular carcinomaILC)组织中细胞粘附分子和雌、孕激素受体（estrogen receptor,ER:progesterone receptor,PR)表达的意义。E -α-catenin,--catenin,γ-catenin和ER、PR的表达。结果：E-cadherin在IDC和ILC中表达缺失和明显减少的分别占18.7%和30%,α-catenin,β-catenin,γ-catenin在IDC中表达缺失和明显减少的分别为75%,43.8%和明显的正相关性;γ-catenin在乳腺浸润性癌中的表达缺失和明显减少与淋巴结转移病例之间有显著的关系。ER和PR在IDC中表达有明显的正相关性。结论：除E-cadherin外,α-catenin,β-catenin,γ-catenin在乳腺浸润性导管癌和浸润性小叶癌中表达明显缺失和减少。γ-catenin表达缺失和明显减少可作为乳腺浸润性癌伴有淋巴结转移的一个预后指标。ER、PR与E-cadherin,α-catenin,β-catenin,γ-catenin可能是乳腺浸润性癌两类独立的预后指标。     

上皮-间叶转变相关蛋白在非小细胞肺癌中的表达及其预后意义

背景与目的:非小细胞肺癌(non-small cell lung cancer,NSCLC)患者最主要的死亡原因是手术后肿瘤转移,而上皮-间叶转变(epithelial-mesenchymal transitions,EMT)是肿瘤发生侵袭、转移的重要原因.本研究探讨EMT相关蛋白Snail、Vimentin、E-cadherin和B-catenin在NSCLC患者中的表达及其预后意义.方法:采用组织芯片技术和免疫组织化学EnvVision两步法检测Snail、Vimentin、E-cadherin和β-catenin蛋白在165例NSCLC患者中的表达情况.根据免疫组织化学结果对NSCLC患者分组,分析Snail、Vimentin、E-cadherin和β-catenin蛋白在判断患者预后和生存情况中的作用.结果:165例NSCLC患者中,Snail、Vimentin、E-cadherin和β-catenin的阳性表达率分别为45.5%、33.9%、66.7%和50.9%.E-cadherin 的表达与Snail呈负相关(P＜0.001),而与β-catenin的表达呈正相关(P=0.003).Snail、Vimentin、E-cadherin/β-catenin复合体异常表达组的生存期均显著低于正常组(P=0.005 9,P=0.025 7,P=0.002 5).上述任意两个蛋白的异常表达是一个独立的预后因素(P＜0.001).结论:EMT相关蛋白Snail、Vimentin和E-cadherin/β-catenin复合体三者中的任意2种蛋白异常表达可作为判断患者预后的独立指标.     

E-cadherinP120ctn在乳腺癌中的表达及意义

  目的  探讨E-钙黏蛋白(E-cadherin, E-cad)、P120连环蛋白(P120ctn)在乳腺浸润性导管癌(IDC)和浸润性小叶癌(ILC)中的表达及其鉴别诊断意义。  方法  收集解放军第113医院2007年12月至2012年5月间有完整随访资料的浸润性导管癌60例、浸润性小叶癌48例及混合性癌20例。采用免疫组织化学S-P法检测E-cad及P120的表达。  结果  E-cad在IDC和ILC中的阳性率分别为85%(51/60)和0, 其差异有统计学意义(P < 0.01);P120在IDC中阳性率为100%, 且均为细胞膜着色, 而在ILC中阳性率亦为100%, 但均为胞浆着色。E-cad和P120联合使用将20例混合癌确诊为IDC 16例及ILC 4例。IDC中E-cad的表达水平与肿瘤分期无关, 与淋巴结转移有关(P < 0.05)。  结论  E-cad和P120联合使用可以鉴别光镜下易混淆的IDC和ILC, 使组织分型更准确, 建议应用于乳腺癌的常规免疫组织化学检测。E-cad的表达水平与淋巴结转移有关。      

肾透明细胞癌组织E-cadherin和β-catenin及Cyclin D1表达的研究

目的:探讨E-cadherin、β-catenin及Cyclin D1在肾透明细胞癌(RCCC)中的表达及意义.方法:用免疫组化法检测E-cadherin、β-catenin及Cyclin D1在67例RCCC组织中的表达情况,并分析其与预后的关系.结果:E-cadherin及Cyclin D1在RCCC组织中表达率分别为35.8％(24/67)和44.8％(30/67).β-catenin在RCCC组织中胞膜和胞质表达率分别为23.9％(16/67)和68.7％(46/67).E-cadherin在RCCC组织中的表达与肿瘤病理分级及临床分期相关(r=0.393,P=0.001;r=0.365,P=0.002).E-cadherin与β-catenin胞膜表达之间具有显著相关性,r=0.531,P=0.000.β-catenin在RC-CC组织中胞膜表达与肿瘤临床分期相关,r=0.386,P=0.001.Cyclin D1与β-catenin胞膜表达之间具有显著相关性,r=0.481,P=0.000.Cyclin D1在RCCC中的表达与肿瘤体积大小具有相关性,r=0.325,P=0.007.结论:E-cadherin和β-catenin蛋白低表达或异常表达与RCCC的病理分级和临床分期有关,并对RCCC预后评价有一定参考意义.     

p16蛋白和E-cadherin表达与鼻咽癌生物学行为的关系

目的:探讨p16蛋白和E-cadherin在鼻咽癌组织中的表达与其生物学行为的关系.方法:应用免疫组化技术检测p16蛋白和E-cadherin在鼻咽癌和鼻咽粘膜炎性组织中的表达.结果:鼻咽癌组织p16蛋白阳性表达率明显低于鼻咽粘膜炎组织(P＜0.05),而两组之间E-cadherin的表达无显著性差异(P＞0.05);Ⅰ、Ⅱ期患者p16蛋白和E-cadherin的阳性表达率高于Ⅲ、Ⅳ期患者,但无统计学差异(P＞0.05);p16蛋白和E-cadherin表达与颈淋巴结转移、远处转移及放疗后复发和转移无明显相关(P＞0.05).结论:p16蛋白表达的缺失可能涉及鼻咽癌的发生、发展过程.E-cadherin表达与鼻咽癌生物学行为的相关性有待进一步研究证实.     

E-cadherin、β-catenin和p120ctn在所谓肺硬化性血管瘤中的表达

背景与目的所谓肺硬化性血管瘤(so-called pulmonary sclerosing hemangioma,PSH)是一种迄今未能确定其组织来源及性质的少见肺部肿瘤,多年来一直是人们研究的热点.本研究通过检测E-cadherin、β-catenin和p120ctn在PSH表面立方细胞和间质多角形细胞的免疫表型以探讨其组织来源.方法采用S P免疫组化法检测25例手术切除PSH标本及8例肺炎性假瘤标本的E-cadherin、β-catenin和p120ctn表达情况.结果25例PSH的立方细胞中,三种上皮粘附分子E-cadherin、β-catenin和p120 ctn均呈胞膜强阳性表达,β-catenin在胞膜强阳性表达的同时有胞质表达.而在多角形细胞中,E-cadherin表达缺失,β-catenin胞膜表达缺失伴部分胞质表达,p120 ctn胞质表达为主伴少量胞膜表达;三种粘附分子在多角形细胞中的表达存在异质性.血管瘤样区的腔内衬细胞E-cadherin、β-catenin和p120 ctn均呈胞质胞膜阳性表达.8例肺炎性假瘤中增生的Ⅱ型肺泡细胞E-cadherin、β-catenin和p120 ctn表达与PSH中立方细胞的表达情况相同.结论PSH中的立方细胞可能是增生的Ⅱ型肺泡细胞,而多角形细胞为肿瘤的实质细胞且缺乏分化成熟的上皮细胞所具有的E-cadherin/catenin复合体.血管瘤样区的腔内衬细胞是与立方细胞相同的上皮细胞而非血管内皮细胞.     

ezrin和E-cadherin在非小细胞肺癌中的表达及意义

背景与目的 有研究表明埃兹蛋白(ezrin)可与上皮钙黏素(E-cadherin)相互作用,参与肿瘤细胞的转移过程.本研究的目的是利用组织芯片技术探讨ezrin和E-cadherin在非小细胞肺癌(NSCLC)组织和淋巴结转移灶中的表达及其意义.方法 应用免疫组织化学LSAB法检测25例良性病变肺组织、287例NSCLC原发灶及120例淋巴结转移灶中ezrin和E-cadherin蛋白的表达.结果 NSCLC原发灶及淋巴结转移灶中ezrin过度表达率分别为57.8%(166/287)和83.3%(100/120),E-cadherin异常表达率分别为82.6%(237/287)和98.3%(118/120),差异均有统计学意义(P=0.000).ezrin过度表达率与病理分级(P=0.005)、转移(P=0.032)有密切关系.E-cadherin异常表达率与病理分级(P=0.024)、转移(P=0.015)、TNM分期(P=0.037)有密切关系.ezrin与E-cadherin表达呈负相关(P=0.029).COX多因素分析显示病理分级、转移、TNM分期、ezrin表达和E-cadherin表达是影响肺癌患者预后的危险因素(P＜0.05).结论 ezrin和E-cadherin可能与肺癌的转移有关;二者有可能作为NSCLC患者临床预后判断的指标.     

微血管密度、p53蛋白和PCNA与肝细胞癌的关系

目的研究肝细胞癌(HCC)内微血管密度(MVD)、p53蛋白与增殖细胞核抗原(PCNA)表达之间的关系.方法采用免疫组化SABC法检测47例人HCC组织的MVD值、PCNA指数和p53蛋白表达情况.结果生存期≥5年者的MVD值(41.19±15.31)明显低于生存期＜5年者的MVD值(54.73±24.72).MVD值与患者的年龄、性别、肿瘤的大小、Edemondson分级无关,也与PCNA指数和p53蛋白表达无直接相关性(P＞0.05).p53蛋白在生存期≥5年及＜5年的2组患者中的异常表达率分别为10.5%和50.0%,有非常显著性差异(P＜0.01),但其与MVD值无关(P＞0.05).低分化HCC的PCNA指数(54.14±14.26)高于高分化HCC的PCNA指数(34.62±6.16),有显著性差异(P＜0.05),但与MVD值无关(相关系数γ=0.082,P＞0.05).结论MVD值和p53基因异常表达均与HCC的5年生存率直接相关,但MVD值、PCNA指数和p53蛋白异常表达相互之间无直接相关性.     

APC、β-catenin、C-myc和Cyclin D1在大肠癌组织中的表达及其意义

背景与目的:Wnt信号转导通路成员各癌基因、抑癌基因的异常,激活下游相关靶基因的转录,在肿瘤发生发展中起重要作用.本研究通过检测不同大肠组织中APC、β-catenin、C-myc和Cyclin D1的表达情况,探讨其在大肠癌发生中的意义.方法:应用免疫组织化学方法检测30例正常大肠粘膜、30例大肠腺瘤、10例大肠腺瘤恶变及50例大肠癌组织中APC、β-catenin、C-myc和Cyclin D1蛋白的表达情况.以β-catenin在细胞膜表达为正常表达,而在胞浆和/或胞核表达为异位表达.结果:大肠癌和大肠腺瘤恶变组织APC阳性率分别为44.0%和40.0%,显著低于大肠腺瘤(86.7%)和正常大肠粘膜(100%)(P＜0.01).大肠癌、大肠腺瘤恶变组织和大肠腺瘤β-catenin胞浆和/或胞核异位表达率分别为62.0%、50.0%、30.0%,均显著高于正常大肠粘膜(0%)(P＜0.01),大肠癌β-catenin异位表达率显著高于大肠腺瘤(P＜0.01).大肠癌、大肠腺瘤恶变组织、大肠腺瘤中C-myc表达率分别为56.0%、60.0%、46.7%,均显著高于正常大肠粘膜(0%)(P＜0.01),而Cyclin D1阳性率分别为66.0%、60.0%、30.0%,均显著高于正常大肠粘膜(0%)(P＜0.01).大肠癌Cyclin D1表达率显著高于大肠腺瘤(P＜0.01).大肠癌中β-catenin异位表达与C-myc和Cyclin D1表达呈正相关关系(r=0.63,P＜0.01;r=0.57,P＜0.01),而与APC表达呈负相关关系(r=-0.39,P＜0.05).结论:大肠癌组织中存在APC低表达和/或β-catenin异位表达,以及C-myc和Cyclin D1的过度表达,4种基因蛋白可能在大肠癌发生过程中起重要作用.     

E-Cadherin Expression Correlates With Histologic Type But Not Tumour Grade in Invasive Breast Cancer

The traditional classification of infiltrating breast carcinomas into ductal and lobular can be diagnosticallychallenging in a small proportion of cases with equivocal histological features and in in-situ lesions withoverlapping features. Distinguishing between the infiltrating ductal (IDC) and lobular (ILC) carcinomas isclinically important because of the different pattern of systemic metastases and prognostic evaluation. E-cadherinis a potentially useful immunohistochemical marker which may serve to differentiate between the two tumourtypes. We therefore studied E-cadherin expression in 32 cases of breast carcinomas comprising 16 IDCs and 16ILCs. The correlation between E-cadherin expression and the histological grade of IDCs was also analysed. Ourresults showed complete loss of E-cadherin expression in all ILCs, while the IDCs consistently showed variableE-cadherin positivity. No significant correlation was found between E-cadherin expression and the histologicalgrade of IDCs. We conclude from this study that E-cadherin is a useful marker to differentiate between IDCand ILC of the breast. A larger study of IDCs is now needed to further evaluate the correlation between Ecadherinand tumour grade to estimate its prognostic potential.     

A comparison of cell cycle markers in well-differentiated lobular and ductal carcinomas

Infiltrating lobular carcinoma (ILC) and infiltrating ductal carcinoma (IDC) are similar in many respects and their histologic features occasionally overlap. Despite the many similarities, some clinical follow-up data and the patterns of metastasis suggest that ILC and IDC are biologically distinct. Unfortunately, most breast cancer research has focused almost exclusively on the ductal subtype or has not stressed the biologic or molecular genetic distinctions between breast carcinoma subtypes. Several reports have suggested the possibility that ILCs and IDCs differ with respect to expression of antigens involved in proliferation and cell cycle regulation. Therefore, we undertook an immunohistochemical evaluation of cell cycle related antigens in ILCs, including histologic variants thought to represent aggressive neoplasms, and IDCs matched for histologic grade (Modified Bloom–Richardson Grade I). We believe that different antigent expression profiles could elucidate the biological distinctiveness of breast carcinoma subtypes and possibly provide diagnostically relevant information. We studied the expression of the following antigents in 28 archived, formalin-fixed ILCs and 34 well-differentiated IDCs: estrogen receptor (ER), progesterone receptor (PR), Her 2-neu, mib-1, cyclin D1, p27, p53, mdm-2 and bcl-2. 94% of ILCs and 100% of IDCs expressed ER; 75% of ILCs and 76% of IDCs expressed PR; 4% of ILCs and 13% of IDCs expressed c cerb B-2; ILCs and IDCs both expressed mib-1 in approximately 10% of lesional cells; 82% of ILCs and 54% of IDCs expressed cyclin D1; 90% of ILCs and 83% IDCs expressed p27 strongly; 4% of ILCs and 4% of IDCs expressed p53, 25% of ILCs and 33% of IDCs expressed mdm-2; 96% of ILCs and 100% of IDCs expressed bcl-2. None of the apparent differences were statistically significant. The ILC variants demonstrated immunophenotypes that were essentially similar to ILCs of the usual type. We conclude that ILCs and well-differentiated IDCs show similar proliferation and cell cycle control antigen profiles. Despite their unusual histologic features, most ILC variants appear to maintain a characteristic ILC immunophenotype.     

Expression of E-cadherin/catenin complexes in breast cancer

Expression of E-cadherin, alpha-, beta- and gamma-catenins were studied in 100 patients with primary breast cancer compiled of 57 invasive ductal carcinomas (IDC) and 43 invasive lobular carcinomas (ILC) by means of immunohistochemistry. Loss of E-cadherin was observed in 26 (45.6%), and alpha-, beta- and gamma-catenin expression was lacking in 22 (38.6%), 27 (47.4%) and 22 (38.6%) IDCs, respectively. The expression in ILCs was significantly lower, as compared to IDCs (p<0.001). Immunostaining of both E-cadherin and catenins was completely lacking in 27 (47.4%) IDCs and 30 (93.8%) ILCs. Go-expression of E-cadherin/beta-catenin or E-cadherin/gamma-catenin was preserved more frequently than that of E-cadherin/alpha-catenin complexes. E-cadherin/catenin complex expression showed significant positive correlation with histological differentiation (p=0.037), ER (p=0.017) and PR expression (p=0.052), and negative correlation with c-erbB-2 receptor overexpression (p=0.046). Patients with tumours showing adhesion complexes containing alpha-catenin had an increased overall survival rate compared to other patients. Expression of either E-cadherin or alpha-catenin only, without the formation of entire adhesion complexes, was not correlated with overall survival. Thus, determination of both E-cadherin and catenins is suggested to add further information to estimate the prognosis of breast cancer patients.     

Invasive lobular carcinoma of the breast has better short- and long-term survival than invasive ductal carcinoma.

The outcome and prognostic factors of 217 women with invasive lobular carcinoma (ILC) and those of 1121 women with invasive ductal carcinoma (IDC) of the breast were compared. The patients were followed up for 10-43 years. Women with ILC had axillary nodal metastases less frequently than those with IDC (43% vs 53%, P = 0.02), although there was no difference in the primary tumour size between the groups. ILCs were more frequently of low grade, had lower mitotic counts and had less tumour necrosis. Furthermore, ILCs had lower S-phase fractions and were more often DNA diploid in flow cytometric analysis than IDCs (P < 0.0001 for all comparisons). The 5- and 30-year corrected survival rates of women with ILC were 78% and 50%, respectively, compared with 63% and 37% for women with IDC (P = 0.001). Small pT1NOMO ILCs (n = 41) had 100% 10-year and 83% 20-year corrected survival rates. In a multivariate analysis, a large primary tumour size, the presence of axillary nodal metastases, a high mitotic count and the presence of tumour necrosis all had an independent prognostic value in ILC. We conclude that ILC is associated with better survival than IDC.     

Genetic alterations in lobular breast cancer by comparative genomic hybridization

Infiltrating lobular carcinoma (ILC) and infiltrating ductal carcinoma (IDC) are distinguished by their histopathological appearance. However, little is known about the differences in genetic changes between lobular cancers and ductal cancers. We used comparative genomic hybridization (CGH) and compared aberrations in 19 ILCs and 46 IDCs. The total number of aberrations was lower in ILC than in IDC. While the average number of DNA copy number losses did not reach significance between them, copy number gains were significantly lower in ILCs. Fifteen of 19 ILCs (79%) showed increased copy number of 1q, and 12 cases (63%) revealed loss of 16q. The presence of these aberrations was independent of nodal status, histologic subtypes (pleomorphic or classic ILC), or BrdUrd-labeling index. ILCs had a higher frequency of 16q loss than did ductal cancers, and a lower frequency of 8q and 20q gains. Our data suggest that the altered growth pattern and clinical presentation which characterize infiltrating lobular cancers are correlated with distinct genetic alterations. Int. J. Cancer 74:513–517, 1997. © 1997 Wiley-Liss, Inc.     

E-cadherin relates to EGFR expression and lymph node metastasis in primary breast carcinoma.

Expression of the calcium-dependent cell-cell adhesion molecule E-cadherin has been examined in 187 primary breast carcinomas using an immunohistochemical technique. The pattern and extent of reactivity has been correlated with clinicopathological data including tumour type, grade and lymph node status and with other prognostic parameters including oestrogen receptor (ER) status, expression of c-erbB-2, pS2 protein and epidermal growth factor receptor (EGFR). Two patterns of E-cadherin staining were observed in carcinomas, membrane reactivity and a diffuse cytoplasmic staining. A marked difference in expression of E-cadherin was observed between infiltrating lobular carcinomas (ILC) and infiltrating ductal carcinomas (IDC), the former showing complete loss of membrane staining, whereas 93% of IDC retained some level of expression. In IDC reactivity was not related to tumour grade but there was a significant association between reduced membrane levels of E-cadherin and the presence of lymph node metastasis, and a highly significant correlation between the presence of cytoplasmic E-cadherin and metastasis. A significant relationship was also demonstrated between reduced E-cadherin reactivity and expression of EGFR. These findings emphasise the complexity of control of E-cadherin in breast carcinomas and provide evidence of a link between membrane signalling pathways and modulation of E-cadherin expression.     

Resection margin status in lumpectomy specimens of infiltrating lobular carcinoma

Aims.To study the status of resection margins in specimens from patients with infiltrating lobular carcinoma (ILC) treated with lumpectomy. Materials and methods.Sixty-six consecutive cases of ILC were compared with the same number of consecutive cases of infiltrating ductal carcinoma (IDC). All cases were treated with lumpectomy. Results.ILCs were divided into 42 cases of typical ILC, 15 variants of ILC (alveolar or solid types) and 9 cases of mixed ILC and IDC. These groups were associated with positive or close resection margins in 22 (52%), 5 (33%) and 3 (33%) cases, respectively. For the group of IDC with partial mastectomies, matched for patient's age and tumor size, positive or close resection margins were observed in 26%. ILCs, measuring less than 2 cm in greatest diameter and having low nuclear grade, had rates of positive or close margins comparable with those of IDC. Typical ILCs, measuring more than 2 cm in diameter, had rates of positive or close margins of 70%. All cases with a positive extensive intraductal component had positive margins. Furthermore, in all types of ILC, tumors with a high nuclear grade tended to be associated with a high rate of positive margins. Conclusions.The status of resection margins in lumpectomy specimens for infiltrating lobular carcinoma is related to the extensive intraductal component status, tumor size and grade, and the presence of variants of ILC or mixed ILC and IDC. Most of these factors can be determined preoperatively by mammography and histopathological evaluation of breast core biopsies, therefore, aiding in planning the surgical strategy of mastectomy.