进展期胃癌HSP90α、CD44v6表达与其临床生物学行为关系的研究

目的:探讨HSP90α、CD44v6在进展期胃癌中的表达特点及其生物学行为,为进展期胃癌的临床治疗提供理论依据.方法:对9 3例进展期胃癌及其5 6例淋巴结转移癌中HSP90α、CD44v6的表达,应用免疫组化方法进行检测.结果:HSP90α在胃癌及淋巴结转移癌中的阳性率分别为54.84%(51/93)、66.07%(37/56).HSP90α在胃癌中表达分别与癌细胞浸润深度、淋巴结转移及TNM分期有关(P＜0.0.5);CD44v6在胃癌及淋巴结转移癌中的阳性率分别为50.54%(47/93)、73.21%(41/56),二者之间的差异显著(P＜0.01).CD44v6在胃癌中的表达分别与癌细胞分化程度、浸润深度、淋巴结转移及TNM分期有关(P＜0.05).结论:进展期胃癌中HSP90α、CD44v6阳性表达与其临床生物学行为尤其是淋巴结转移密切相关,患者可能预后较差,应采取积极的综合治疗措施.     

胃癌及癌前病变组织中CD44v6表达的意义

目的探讨CD44v6基因表达与胃癌发生及胃癌生物学行为的关系.方法应用抗CD44v6蛋白的单克隆抗体,采用免疫组化ABC方法对正常胃粘膜(n=10)、各级胃粘膜异型增生(轻度n=16,中度n=12,重度n=14)、早期胃癌(n=16)及进展期胃癌(n=52)进行研究,并与胃癌类型、大小、有无淋巴结转移等作了比较分析.结果正常胃粘膜CD44v6为阴性,随着胃粘膜病变的进展,CD44v6蛋白的表达率逐渐升高,至进展期胃癌,表达率达到顶峰.轻、中、重度异型增生表达率分别为12%,33%,43%;早期胃癌及进展期胃癌的表达率分别为44%和73%.各级异型增生表达率之间的差异无显著性,而进展期胃癌表达率显著高于早期胃癌(P＜0.05),淋巴结转移组的表达率显著高于淋巴结未转移组(82%vs56%,P＜0.05),肠型胃癌的表达率高于弥漫型胃癌(78%vs56%,P＜0.05),CD44v6蛋白的表达与胃癌肿块大小无相关性.结论胃粘膜重度异型增生在CD44v6基因表达上已具有明显的潜在恶性趋势,CD44v6基因表达阳性的胃癌具有更强的浸润及淋巴结转移的能力.     

胃癌中Ezrin,E-cadherin及CD44的表达及意义

目的:检测Ezrin及细胞黏附分子E-cadherin、CD44在胃癌细胞的表达,了解Ezrin对瘤细胞黏附分子调节及对胃癌浸润生长的影响.方法:手术切除胃癌标本80例(其中62例附癌旁胃组织)行Ezrin、E-cadherin和CD44v6免疫组化染色.结果:Ezrin的表达与胃癌的转移呈正相关,与分化程度呈负相关(均P＜0.05).CD44的表达与胃癌的浸润深度,淋巴结转移呈正相关,与分化程度呈负相关(均P＜0.05).E-cadherin的表达与胃癌的浸润深度、转移及分化程度呈负相关(均P＜0.05).Spearman等级相关分析显示,Ezrin与CD44的表达呈显著正相关(r5=0.305,P＜0.05),Ezrin与E-cadherin的表达呈负相关(r5=-0.314.P＜0.05).结论:胃癌组织Ezrin增加与肿瘤细胞的分化有关,并可调节E-cadherin、CD44而影响胃癌细胞的黏附性.     

进展期胃癌HSP900α、CD44v6表达与其临床生物学行为关系的研究

目的:探讨HSP90α、CD44v6在进展期胃癌中的表达特点及其生物学行为,为进展期胃癌的临床治疗提供理论依据. 方法: 对93例进展期胃癌及其56例淋巴结转移癌中HSP90α、CD44v6的表达,应用免疫组化方法进行检测. 结果:HSP90α在胃癌及淋巴结转移癌中的阳性率分别为54.84% (51/93)、66.07%(37/56).HSP90α在胃癌中表达分别与癌细胞浸润深度、淋巴结转移及TNM分期有关(P<0.05); CD44v6在胃癌及淋巴结转移癌中的阳性率分别为50.54% (47/93)、73.21%(41/56),二者之间的差异显著(P<0.01). CD44v6在胃癌中的表达分别与癌细胞分化程度、浸润深度、淋巴结转移及TNM分期有关(P<0.05). 结论:进展期胃癌中HSP90α、CD44v6阳性表达与其临床生物学行为尤其是淋巴结转移密切相关,患者可能预后较差,应采取积极的综合治疗措施.     

胃癌组织中Ezrin、CD44V6、E-钙黏附素的表达及意义

采用免疫组化SP法检测78例胃癌组织、30例胃良性病变组织、30例正常胃组织中的Ezrin、CD44V6、E-钙黏附素的表达.发现胃癌组织中Ezrin、CD44V6蛋白表达阳性率显著高于胃良性病变及正常胃组织(P＜0.01),有淋巴结转移组明显高于无淋巴结转移组(P＜0.05),T3、T4期明显高于T1、T2期,Ⅲ、Ⅳ期明显高于Ⅰ、Ⅱ期(P＜0.05).E-钙黏附素蛋白表达阳性率显著低于胃良性病变及正常胃组织(P＜0.01);无淋巴结转移组明显高于有淋巴结转移组(P＜0.01),T1、T2期明显高于T3、T4期,Ⅰ、Ⅱ期明显高于Ⅲ、Ⅳ期(P＜0.05).胃癌组织中Ezrin与CD44V6蛋白表达水平呈正相关(γ=0.81,P＜0.05),与E-钙黏附素蛋白表达水平呈负相关(γ=-0.126,P＜0.05).联合检测胃癌组织中的Ezrin、CD44V6、E-钙黏附素蛋白有助于胃癌转移的判断.     

整合素α2β1及CD44v4在胃癌组织中的表达及意义

目的讨论整合素α2β1和CD44v4在胃癌组织中的表达及意义。方法采用免疫组化SP法检测85例胃癌标本和50例癌旁正常胃组织中整合素α2β1和CD44v4的表达情况,分析二者的表达与胃癌生物学行为以及它们之间的相关性。结果①整合素α2β1与CD44v4在胃癌标本中的阳性表达率均高于癌旁正常组织(P<0.05)。②整合素α2β1和CD44v4在胃癌中的表达与胃癌的分化程度、TNM分期、淋巴结转移和浸润深度有关(P<0.05)。③整合素α2β1和CD44v4在胃癌中的表达呈正相关(r=0.517,P<0.05)。结论整合素α2β1和CD44v4在胃癌中高表达且在胃癌的浸润、转移过程中起正协同作用,并且与胃癌的分化程度、TNM分期、淋巴结转移和浸润深度密切相关,与患者的年龄、性别以及病理组织学类型无关。     

VEGF、CD44v6及p27在胃癌组织中的表达及其临床意义

目的探讨血管内皮细胞生长因子(VEGF)、CD44v6及p27在胃癌中的表达并判断其与胃癌发生的关系。方法应用S-P法,对63例胃癌组织及相应的癌旁组织、28例正常胃组织进行VEGF、CD44v6及p27蛋白检测,并研究其与病理分期的相关性。结果胃癌组织中p27阳性表达率显著下降,VEGF、CD44v6阳性表达率显著升高(P0.05);胃癌组织中,分化程度低、侵及浆膜、有淋巴结转移及TNM分期高者,p27阳性表达率显著下降,VEGF、CD44v6阳性表达率显著升高(P0.05);胃癌中VEGF表达与p27表达呈负相关(r=-0.614 P0.05);与CD44v6表达呈正相关(r=0.614 P0.05);p27的表达与CD44v6表达呈负相关(r=-0.745 P0.05)。结论 VEGF、CD44v6及p27表达与胃癌发生发展、浸润、转移有关,预示这三种蛋白的表达可能与胃癌的治疗和预后具有显著关系,为临床治疗胃癌提供新的思路。     

胃癌及癌前病变组织CD44V6表达的研究

目的:检测细胞粘附分子(CD44V6)在胃癌及癌前病变的表达,探索其与胃癌的发生、转移及预后的相关性.方法:用免疫组化方法检测30例浅表性胃炎,34例中重度萎缩性胃炎、34例不典型增生胃粘膜及64例胃癌组织中的CD44V6的表达.结果:CD44V6的阳性表达率在浅表性胃炎、中重度萎缩性胃炎、不典型增生胃粘膜及胃癌组织分别为3.33%(1/30)、14.71%(5/34)、44.12%(15/34)及60.94%(39/64).不典型增生及胃癌组阳性率明显高于浅表性胃炎组及中重度萎缩性胃炎组(均P＜0.01),中重度萎缩性胃炎与浅表性胃炎组比较差异无统计学意义;CD44V6的表达与胃癌的远处转移有关(P＜0.05),与TNM分期有关(P＜0.01),与淋巴结转移无关,与性别、肿瘤大小、大体类型、组织学分型、浸润深度间差异均无统计学意义.结论:用免疫组织化学方法检测胃活检标本中的CD44V6可能有助于胃癌早期诊断和远处转移趋势推测.     

CD44v6基因变异体在胃癌中的表达及其临床意义

目的探讨胃癌中CD44v6基因变异体的表达及其临床意义.方法①手术切除胃癌标本80例,有淋巴结转移60例,无淋巴结转移20例,正常对照胃标本10例.10%中性Formalin固定,石蜡包理,常规切片,HE染色,光学显微镜观察,组织病理学诊断,用世界卫生组织(WHO)1979年提出的分型法分型.②免疫组织化学方法切片厚4μm,高温修复抗原,用鼠抗人CD44v6单克隆抗体(MAB-0038),链霉素抗生素蛋白-过氧化酶免疫组化染色试剂盒(irmmunostain streptavidin-peroxidase, SPkit)(迈新公司提供)处理切片,光学显微镜观察.③免疫组化结果判定阳性表达产物定位于细胞膜,着色棕黄至棕褐色,反应强度分为弱阳性、阳性、强阳性.结果CD44v6阳性物质位于细胞膜上,呈棕黄色至棕褐色,正常粘膜不表达,间质不着色.20例无淋巴结转移标本中10例阴性(50.0%),8例弱阳性(40.0%),2例阳性(10.0%);60例有淋巴结转移的标本中,9例阴性(15.0%),51例阳性(85.0%),其中8例弱阳性(13.3%),10例阳性(16.7%),强阳性33例(55.0%).有淋巴结转移与无淋巴结转移两组间的表达结果有显著性差异(P<0.001).提示CD44v6基因变异体表达与胃癌淋巴结转移关系密切.CD44v6在不同组织类型的胃癌间和肿瘤不同浸润深度间的表达与否,表达强度无统计学意义(P>0.05%).结论CD44v6可作为预测胃癌淋巴结转移潜能可靠的分子标记物.     

CD44v6在胰腺癌组织中的表达及其临床意义

目的探讨CD44v6蛋白表达与胰腺癌增殖及淋巴结转移的关系.方法应用免疫组织化学(S-P)法检测38例胰腺癌组织标本中CD44v6和PCNA的表达.结果 CD44v6在胰腺癌中的阳性率为65%(25/38),与淋巴结转移呈非常显著相关(P<0.01),与肿瘤分化程度无关(P>0.05).CD44v6阳性染色者胰腺组织中PCNA标记率较阴性者高(P<0.05).结论 CD44v6在胰腺癌的增殖、转移过程中可能起重要作用,可作为胰腺癌预后预测的生物学指标之一.     

CD44v6 in peripheral blood and bone marrow of patients with gastric cancer as micro-metastasis

AIM:To detect the expression of CD44 correlated withthe ability of micro-metastasis in peripheral blood andbone marrow of patients with gastric cancer and to de-duce its clinical significance.METHODS:Preoperative peripheral blood and bonemarrow specimens from 46 patients with gastric cancerand 6 controls were studied by semi-quantitative RT-PCR amplification of CD44v6mRNA.Preoperative andpostoperative peripheral blood specimens from 40patients with gastric cancer and 14 controls were studiedby quantitative RT-PCR amplification of CD44v6rnRNA inthe corresponding period.RESULTS:Semi-quantitative RI-PCR amplificationshowed that CD44v6mRNA expression of peripheralblood and bone marrow was positive in 39 (84.8%)and 40 (86.9%) of 46 patients with gastric cancer,respectively.In peripheral blood,CD44v6mRNAexpression was positive for diffuse type in 30 (93.8%)of 32 patients and for intestinal type in 9 (64.3%)of 14 patients.On the other hand,in bone marrow,CD44v6mRNA expression was positive for diffuse typein 31 (96.9%) of 32 patients and for intestinal typein 10 (71.4%) of 14 patients.There was a significantdifference between the diffuse type and intestinal type.Quantitative RT-PCR amplification demonstrated thatCD44v6mRNA was not expressed in the peripheral bloodof controls and CD44v6mRNA expression was positivefor preoperative peripheral blood in 40 patients withgastric cancer,the expression levels being from 4.9×102 to 3.2×10~5 copies/g RNA.The average expressionlevel of CD44v6mRNA in peripheral blood was 3.9×10~(10) copies/g RNA.The expression levels of CD44v6mRNAin peripheral blood in gastric cancer patients aftercurative operation increased from 5.5×100 to 7.6×10copies/g RNA (P=0.00496).After curative operation,theexpression level decreased markedly.CONCLUSION:Semi-quantitative and quantitative RT-PCR amplification for CD44v6mRNA is a sensitive andspecific method for the detection of micro-metastasis inperipheral blood and bone marrow,which might be usedas an indicator of tumor burden and therapeutic effect.     

应用组织芯片研究凋亡抑制基因Survivin在胃癌中的表达

目的　检测Survivin和CD44v6在胃癌中的表达,以探讨二者在胃癌中表达的相关性及其与预后的关系。方法　利用组织芯片技术构建胃癌组织芯片,应用免疫组织化学S P法检测Survivin和CD44v6蛋白在胃癌中的表达。结果　胃癌中Survivin及CD44v6的总表达率分别为 58 6% (58 /99)和 35 4% (35 /99)。Survivin在早期胃癌中的表达显著高于进展期胃癌 (P<0 05 ),与胃癌的其它临床病理特征无相关性。CD44v6阳性表达与胃癌生长方式(P<0 001)、浸润深度 (P<0 05 )及淋巴结转移 (P<0 001 )密切相关。Sur vivin和CD44v6在胃癌中的表达无相关性(r=-0 065,P>0 05)。Survivin与胃癌患者的生存率无显著相关,而CD44v6表达阳性组 5年生存率(16 13% )显著低于CD44v6表达阴性组 5年生存率(60 67% ) (P<0 001 )。结论　Survivin和CD44v6在胃癌中均有过量表达。Survivin可能参与胃癌发生、发展的早期过程;而CD44v6阳性表达与胃癌的浸润和转移密切相关,同时可以提示胃癌的不良预后。     

胃癌患者血清及癌组织中CD44v6表达及意义

[目的]检测胃癌患者血清及胃癌组织中CD44v6的表达及其与胃癌临床病理特征间的关系,进一步阐述CD44v6在胃癌发生发展中的作用。[方法]收集40例经病理证实的胃癌患者,20例正常健康体检者为对照组,20例取自距癌组织边缘5cm以上癌旁胃黏膜标本。采用双抗体夹心-酶联免疫吸附法检测40例胃癌患者术前和20例正常健康者血清中CD44v6水平,免疫组化SP法测定40例经手术切除的胃癌组织标本和20例癌旁胃黏膜标本中CD44v6的表达。[结果]①胃癌患者血清中CD44v6[(177.21±46.48)μg/L]高于正常健康者(P<0.01)。②癌组织中CD44v6的阳性表达率为77.5%,显著高于癌旁胃黏膜中的表达(P<0.01),CD44v6在血清和组织中的表达随组织学分级、临床分期的增高及有无淋巴结转移而升高,呈正相关性。[结论]CD44v6参与了胃癌的发生,并且可反映机体肿瘤的负荷状态及预测肿瘤的进展;检测CD44v6的血清含量可能为胃癌的诊断提供依据。     

胃癌中CD15s抗原和CD44v6基因蛋白的表达及其意义

[目的 ]探讨唾液酸化的路易斯寡糖 X(CD15s)抗原和CD4 4v6基因蛋白表达与胃癌临床病理指标和患者预后的关系。 [方法 ]应用高敏感性的催化信号放大免疫组化技术 ,对早期胃癌 17例、中期胃癌 2 1例和晚期胃癌5 7例组织进行CD15s抗原和CD4 4v6蛋白检测 ,并结合肿瘤的病理学指标和临床随访资料进行分析。 [结果 ]在胃癌中 ,CD15s和CD4 4v6的表达阳性率分别为 86 .3%和 82 .1%。且晚期胃癌明显高于早、中期胃癌 (P <0 .0 5 )。CD15s和CD4 4v6表达水平具有一致性 ,均与胃癌浆膜浸润、淋巴结转移和患者预后呈正相关 (P <0 .0 5 )。 [结论 ]CD15s和CD4 4v6表达与胃癌转移和患者生存期密切相关 ,检测CD15s和CD4 4v6的表达可作为判断胃癌预后的参考指标。     

胃癌及淋巴结转移灶中CD44v6和上皮钙粘素的表达及其意义

目的 :探讨 CD4 4 v6和上皮钙粘素 (E- cd)在胃腺癌及淋巴结转移灶中的表达及其意义。方法 :应用免疫组化 SABC法检测 2 0例正常胃粘膜 ,2 0例异形增生 ,185例胃癌原发灶及 10 9例淋巴结转移灶中 CD4 4 v6和 E- cd表达。结果 :CD4 4 v6和 E- cd在异型增生、胃癌原发灶及淋巴结转移灶中阳性表达率分别为 2 0 .0 0 % (4/ 2 0 )、66.4 9% (12 3 / 185 )和87.18% (10 2 / 10 8)以及 85 .0 0 % (17/ 2 0 )、5 2 .97% (98/ 185 )和 2 6.5 0 % (3 1/ 117)。三者之间有显著差异 (P<0 .0 1)。CD4 4 v6表达率与胃癌生长方式、组织学类型、血管淋巴管内浸润及 TNM分期无关。 E- cd阳性表达与胃癌生长方式、组织学类型及 TNM分期显著相关。早期肠型胃癌 CD4 4 v6阳性表达率显著高于弥漫型 (P<0 .0 5 ) ,在进展期胃癌则无显著差异。E- cd的阳性表达率下降主要见于弥漫型胃癌。结论 :CD4 4 v6和 E- cd阳性表达同胃癌分化及生物学行为密切相关 ,是预测其侵袭转移有价值的指标。同时 ,此结果也支持胃癌两种不同起源的假说。     

Expression of epidermal growth factor receptor and CD44 splicing variants sharing exons 6 and 9 on gastric and esophageal carcinomas: a two-color flow-cytometric analysis

Quantitative analysis based on the percentage of positive cells by two-color flow cytometry was used to quantify the surface expression of epidermal growth factor receptor (EGFR), and exons v6 and v9 of CD44 splice variants on tumor. Almost all patients with primary gastric and esophageal carcinomas, and benign mucosa of the stomach and esophagus showed usually high levels of EGFR expression, a mean of approximately 60% of cells being positive. Metastatic gastric carcinoma showed significantly higher levels of EGFR expression, a mean of 80% of cells being positive. Reduced expression of EGFR was observed in irradiated esophageal carcinoma. Adenocarcinomas, including primary and metastatic lesions, or cancer cell lines of the stomach revealed consistently very low or undetectable levels of expression of exon v6 of the CD44 variant (CD44v) protein. However, CD44v containing exon v9 could be detected in normal gastric epithelium and primary gastric carcinoma as well as in six adenocarcinoma cell lines. Exon v9 is significantly overexpressed on metastatic adenocarcinoma cells obtained from malignant ascites. On the other hand, normal squamous epithelium and primary squamous cell carcinoma (SCC) of the esophagus, and two SCC cell lines showed coexpression of exons v6 and v9 of CD44v. The expression of the CD44v6 molecule was significantly reduced in the irradiated primary SCC, although CD44v9 expression on the primary SCC remained unchanged after the radiation therapy. These results suggest that up-regulation of EGFR and CD44v9 molecules on gastric carcinomas, especially metastatic adenocarcinomas, shows tumor growth and tumor progression. In addition, down-regulation of EGFR and CD44v6 molecules on irradiated esophageal carcinoma may be involved in the mechanisms suppressing tumor growth and metastatic potential. Received: 24 June 1998 / Accepted: 1 September 1998     

Expression of CD44 and its variants on gastric epithelial cells of patients with Helicobacter pylori colonisation.

BACKGROUND--Studies have suggested that expression of the adhesion molecule CD44 may be of prognostic importance in gastric cancer. In addition, there is strong evidence that Helicobacter pylori has a role in gastric cancer. AIMS--To determine the expression of CD44 and its variants (v6, v9) and HLA class II molecules on human gastric epithelial cell and intraepithelial lymphocytes in patients with and without H pylori infection. PATIENTS--Eighteen patients (seven men and 11 women) attending for endoscopic evaluation because of upper gastrointestinal symptoms were included. An additional 10 patients (five men and five women) were analysed for CD44 variant expression). METHODS--Biopsy specimens were taken from the gastric antrum during endoscopy. Gastric epithelial cells and intraepithelial lymphocytes were examined by two colour flow cytometry and compared in patients with and without H pylori infection. RESULTS--Expression of CD44 and its variants (CD44 v9) was increased in epithelial cells but not in intraepithelial lymphocytes. Both epithelial cells and intraepithelial lymphocytes expressed higher levels of HLA class II molecules (DR and DP), possibly as a result of local cytokine production. Furthermore, results showed upregulation of CD44 on a gastric epithelial cell line (AGS) by cytokines and peripheral blood mononuclear cell supernatant. CONCLUSIONS--These data suggest that H pylori, either directly or through a local inflammatory response, is responsible for increased expression of CD44 and its variant CD44 v9. These data are of potential importance in relation to increased expression of CD44 and CD44 v9 on gastric carcinoma.     

Expression and significance of CD44s, CD44v6, and nm23 mRNA in human cancer

AIM: To investigate the relationship between the expression levels of nm23 mRNA, CD44s, and CD44v6,and oncogenesis, development and metastasis of human gastric adenocarcinoma, colorectal adenocarcinoma,intraductal carcinoma of breast, and lung cancer.METHODS: Using tissue microarray by immuhistochemical (IHC) staining and in situ hybri-dization (ISH), we examined the expression levels of nm23mRNA, CD44s, and CD44v6 in 62 specimens of human gastric adenocarcinoma and 62 specimens of colorectal adenocarcinoma; the expression of CD44s and CD44v6in 120 specimens of intraductal carcinoma of breast and 20 specimens of normal breast tissue; the expression of nm23 mRNA in 72 specimens of human lung cancer and 23 specimens of normal tissue adjacent to cancer.RESULTS: The expression of nm23 mRNA in the tissues of gastric and colorectal adenocarcinoma was not significantly different from that in the normal tissues adjacent to cancer (P＞0.05), and was not associated with the invasion of tumor and the pathology grade of adenocarcinoma (P＞0.05). However, the expression of nm23 mRNA was correlated negatively to the lymph node metastasis of gastric and colorectal adenocarcinoma (r = -0.49, P＜0.01; r = -4.93, P＜0.01). The expression of CD44s in the tissues of gastric and colorectal adenocarcinoma was significantly different from that in the normal tissues adjacent to cancer (P＜0.05;P＜0.01). CD44v6 was expressed in the tissues of gastric and colorectal adenocarcinoma only, the expression of CD44v6 was significantly associated with the lymph node metastasis, invasion and pathological grade of the tumor (r = 0.47, P＜0.01; r = 5.04, P＜0.01). CD44sand CD44v6 were expressed in intraductal carcinoma of breast, the expression of CD44s and CD44v6 was significantly associated with lymph node metastases and invasion (P＜0.01). However, neither of them was expressed in the normal breast tissue. In addition, the expression of CD44v6 was closely related to the degree of cell differentiation of intraductal carcinoma of breast (x2= 5.68, P＜0.05). The expressional level of nm23mRNA was closely related to the degree of cell differentiation (P＜0.05) and lymph node metastasis (P＜0.01), but the expression of nm23 gene was not related to sex, age, and type of histological classification (P＞0.05).CONCLUSION: Patients with overexpression of CD44s and CD44v6 and low expression of nm23 mRNA have a higher lymph node metastatic rate and invasion. In addition, overexpression of CD44v6 is closely related to the degree of cell differentiation. Detection of the three genes is able to provide a reliable index to evaluate the invasion and metastasis of tumor cells.