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.     

CD44V6和CD44S表达与膀胱癌转移的相关性研究

采用免疫组化ＳＡＢＣ法对８１例膀胱移行细胞癌患者癌组织中细胞粘附分子ＣＤ４４ｖ６和ＣＤ４４ｓ的表达进行检测。结果显示,ＣＤ４４ｖ６的阳性表达与膀胱癌临床分期、病理分级有显著关系,伴淋巴结转移组的ＣＤ４４ｖ６阳性表达率显著低于未转移组。     

CD44V6基因在前列腺癌组织中的表达及其意义

目的　探讨CD4 4V6 基因与前列腺癌 (PCa)的发生、转移及预后的关系。方法　采用S P免疫组织化学方法检测 82例PCa组织中CD4 4V6 基因的表达情况。结果　CD4 4V6 基因在前列腺癌中有较高的表达 ,阳性率为 46 3 % (38/82 ) ,其中伴盆腔淋巴结转移或骨转移者阳性率为62 5 % (1 5/2 4 ) ,无转移者阳性率 37 9% (2 3/58) ,两者具有显著性差异 (P <0 0 1 )。CD4 4V6 在PCa组织中的高表达还与癌组织的Gleason评分及预后有关 (P <0 0 5)。结论　具有CD4 4V6 高表达的PCa具有更强的浸润和转移能力 ,恶性度较高 ,分化较差 ,CD4 4V6 可作为判断预后及指导术后治疗的一项重要指标。     

CD44V6在人类大肠癌细胞中的表达及其对细胞骨架的影响

目的研究 CD44V6在人类大肠癌细胞中的表达及其对细胞骨架的影响,探讨 CD44V6影响肿瘤转移的作用机理。方法应用原位 RT-PCR 分子杂交、免疫组化、免疫荧光定量分析的方法研究 CD44V6在人类大肠癌细胞及大肠癌组织中的表达,应用免疫荧光及共聚焦三维图象重构分析的方法,研究 CD44V6对大肠癌细胞的细胞骨架的影响。结果 CD44V6在 HT29、Lovo 细胞中均有表达,不管在 mRNA 水平还是在蛋白质水平,高转移能力的 Lovo 细胞表达 CD44V6均高于低转移能力的 HT29细胞。将 HT29、Lovo 细胞用 CD44V6单抗封闭则发现 CD44V6能使 HT29、Lovo 细胞的细胞骨架发生改变。结论 CD44V6的表达与大肠癌细胞的转移潜能有关。CD44V6能影响大肠癌细胞骨架的构像和分布。从而影响大肠癌细胞的运动能力而促进大肠癌转移。     

CD44和埃兹蛋白在散发性结、直肠癌转移中的作用及临床意义

目的研究CD44和埃兹（Ezrin）蛋白在散发性结、直肠癌转移组及未转移组中的表达、相互关系及临床意义。方法应用En Vision免疫组化法检测132例散发性结、直肠癌（转移组74例、未转移组58例）中CD44和埃兹蛋白的表达，将二者分别与患者的临床病理参数进行统计分析并评估二者的相关性，同时进行单因素和多因素生存分析。结果CD44在转移组中的阳性率（71.6％）高于未转移组（53，4％，P=0.031）。埃兹蛋白在转移组中的阳性率（86．5％）亦高于未转移组（70．7％，P=0.026）。CD44和埃兹蛋白共表达率转移组（63．5％）高于未转移组（43．1％，P=0．019）。二者在结、直肠癌中的表达呈正相关（P=0．020，r=0．202）。二者均与患者年龄、性别、肿瘤大小、部位、分化程度、浸润深度等临床病理参数无关（P〉0．05）。单因素生存分析显示，CD44阳性、埃兹蛋白阳性及二者共表达均与患者的无病生存率相关（P〈0．05）。多因素生存分析显示，CD44、埃兹蛋白共表达是结、直肠癌独立的预后影响因子（P〈0．05）。结论CD44和埃兹蛋白的表达与结、直肠癌转移密切相关，在结、直肠癌发生发展过程中起协同作用，二者均为阳性表达的患者无病生存率低于阴性表达者，CD44和埃兹蛋白共表达对于评估散发性结、直肠癌的预后有一定的价值。     

结直肠癌组织中ESA和CD44的表达及其临床病理意义

目的:探讨原发性结直肠癌组织中E SA和CD44蛋白表达的关系及临床病理意义.方法:应用免疫组织化学SP法检测10例正常结直肠黏膜组织、13例伴不典型增生的结直肠腺瘤及67例结直肠癌组织中ESA和CD44的表达,并比较两者不同病理参数的相关性.结果:结直肠癌组织中ESA和CD44的表达明显高于其在正常肠黏膜组织和伴不典型增生的结直肠腺瘤中的表达( P<0.05); 在结直肠癌中,CD44的表达与淋巴结转移,分化程度及Dukes分期有关(χ2 = 8.375,14.284,7.948,均P<0.05); ESA与年龄、浸润深度、分化程度及Dukes分期有关(χ2 = 16.918,15.195,10.395,7.681,均P<0.05); ESA的表达与CD44的表达呈正相关( r = 0.614,P = 0.000).结论:ESA与CD44在结直肠癌的发生发展、浸润转移中密切相关,同步检测二者在结直肠癌组织中的表达并综合分析两者之间的关系对评价结直肠癌的侵袭转移能力判断具有一定价值.     

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相关（P＜0．01），与胰分化程度无关（P＞0．05）。CD44v6阳性染色胰腺组织中PCNA标记率较阴性高（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。     

肺癌患者血清中可溶性CD44V6含量及组织中CD44V6表达的临床意义

目的 探讨肺癌患者血清中可溶性CD44V6(SCD44V6)蛋白含量及癌组织中CD44V6蛋白表达的临床意义。方法 应用ELISA及免疫组化ABC技术，检测肺癌患者血清中及癌组织内CD44V6，同时与健康人对照。结果 肺癌患者血清中CD44V6含量明显高于健康对照组，术前高于术后，复发转移组高于对照组，CD44V6的血清含量及组织表达与T分期无关，与N分期密切相关。结论 血清中CD44V6含量及组织中CD44V6蛋白表达与肺癌的转移复发有关．可作为一种可靠的判断手术疗效、预后及复发转移的临床检测指标。     

明胶酶、CD44v6在结直肠癌中的表达及意义

目的探讨明胶酶在结直肠癌中的表达及其CD44v6在结直肠癌侵袭转移过程中的关系。方法采用明胶酶谱（gel zymography）和S-P免疫组化对50例结直肠癌癌组织和相应正常组织中的明胶酶、CD44v6进行检测。结果明胶酶在结直肠癌中的表达水平显著高于正常组织（P〈0．05）；明胶酶与结直肠癌的Duke’s分期呈同步的正相关（P〈0．05）；明胶酶在CD44v6强阳性组中表达量升高显著（P〈0．05）。结论明胶酶与结直肠癌的侵袭转移性有着密切的关系，不仅在癌细胞的酶解，而且在癌细胞的黏附、运动过程中有可能发挥着重要作用。     

大肠癌组织RAB5A和CD44v9表达的意义

目的:探讨大肠癌组织RAB5A和CD44v9表达的意义．方法:应用SP免疫组化法检测43例大肠癌病理蜡块中RAB5A和CD44v9的蛋白质表达;取 60例大肠癌患者新鲜组织标本,提取RNA并逆转录合成cDNA,应用Real-time PCR法检测组织样本中RAB5A和CD44v9的基因表达;分析CD44v9和RAB5A的基因与蛋白质表达量与大肠癌分化及转移程度的相关性．结果:RAB5A蛋白表达阳性率为100％,阳性表达位于胞质和胞膜;CD44v9表达阳性率为 86．7％,阳性表达位于胞质;荧光定量PCR结果经熔解曲线分析各样本扩增产物的Tm值一致并与阳性对照的Tm值吻合．RAB5A cDNA 的表达量在高分化和中分化大肠癌组织中低于低分化大肠癌组织(P<0．01),在无淋巴结转移的大肠癌组织中低于有淋巴结转移的组织(P<0．01),而CD44v9 cDNA的表达趋势与 RAB5A相同;RAB5A与CD44v9的蛋白和基因表达均呈正相关(x2=14．532,P<0．01)．结论:RAB5A和CD44v9的表达与大肠癌的分化和转移有关,可能在跨膜信号传导和基质侵袭中共同发挥作用．     

食管癌中桩蛋白、CD44V6的表达及意义

目的探讨桩蛋白（Paxillin）和CD44V6在食管癌组织中的表达及其与食管癌生物学行为的关系。方法采用免疫组化SP法检测食管癌组织中Paxillin和CD44V6的表达及两者的相关性。结果Paxillin和CD44V6在食管鳞癌和腺癌中的表达高于食管正常黏膜（P〈0．01）;Paxillin和CD44V6在食管鳞癌中表达与临床分期（P〈0．01）、浸润深度（P〈0．01）和淋巴结转移（P〈0．05）有关;Paxillin和CD44V6在食管鳞癌中表达无相关性（P〉0．05）。结论Paxillin和CD44V6的表达在食管鳞癌的侵袭转移过程中发挥着重要的作用,可作为反映食管癌肿瘤生物学指标和抗肿瘤治疗的靶点。     

食管癌中细胞粘附分子E-钙粘素和CD44变异体表达及其临床意义

目的　探讨细胞粘附分子E 钙粘素 (E CD)和CD44变异体 (CD44V6)的表达与食管癌临床病理及预后的关系。方法　对 5 8例食管癌标本应用SP免疫组化染色法进行E CD、CD44V 6检测 ,并对其中 42例进行术后 3年随访。结果　E CD低表达和CD44V 6高表达与食管癌的浸润转移、复发和预后相关 (P <0 .0 5 )。E CD低阳性表达率与食管癌细胞分化程度相关 (P <0 .0 5 )。食管癌中E CD和CD44V6的表达无相关性 (P >0 .0 5 )。结论　E CD和CD44V 6在食管癌中的表达与食管癌的发生发展、侵袭转移和预后密切相关 ,E CD和CD44V6在食管癌中的表达无相关性 ,在食管癌的发生、发展、侵袭转移中是 2个独立的调节因子 ,可视为预测侵袭转移和估计预后的重要参考指标     

KAI1和CD44v6在骨肉瘤中的表达及意义

目的探讨KAI1和CD44v6蛋白在骨肉瘤中的表达及其与临床病理特征及预后的关系。方法应用免疫组织化学SP法,检测87例骨肉瘤组织中KAI1和CD44v6蛋白的表达,用Cox风险回归模型评价骨肉瘤患者预后独立因素。结果KAI1蛋白与肿瘤的分化程度、远处转移相关,而CD44v6仅与远处转移相关。骨肉瘤KAI1和CD44v6的表达无相关性。Cox模型分析显示影响骨肉瘤患者预后因素是KAI1表达、远处转移和Enneking外科分期。结论KAI1和CD44v6的异常表达参与了骨肉瘤的转移过程,KAI1表达、远处转移、Enneking外科分期是预测骨肉瘤患者预后的独立因素。     

Clinical significance of serum levels of CD44 variant exons 8–10 protein in colorectal cancer

We examined serum levels of a CD44 splice variant that contained variant exons 8–10 (CD44v8–10) as a tumor marker in colorectal cancer patients. We performed enzyme-linked immunosorbent assays in 81 sera obtained from 71 colorectal cancer patients and 10 healthy controls. Serum CD44v8–10 levels were significantly higher in the colorectal cancer patients than in the healthy controls (0.209 ± 0.098 versus 0.114 ± 0.019 OD; P < 0.01). There was a close correlation between immunohistochemical expression and serum CD44v8–10 levels. Surgical resection of the tumors resulted in a reduction of serum CD44v8–10 levels. There was no significant correlation between serum CD44v8–10 level and serosal invasion or histologic type. However, a significant correlation was observed between serum CD44v8–10 level and lymphatic or venous invasion. In addition, serum CD44v8–10 levels were significantly higher in carcinomas associated with lymph node or liver metastasis than in those without metastasis. These findings suggest the usefulness of serum CD44v8–10 level in the prediction of colorectal cancer metastasis. (Received July 25, 1997; accepted Nov. 28, 1997)     

黏附分子CD44变异剪接体6在甲状腺肿瘤中的表达及其临床意义

目的　探讨CD44变异剪接体 6(CD44V6 )在甲状腺肿瘤组织的表达情况及其与肿瘤发生、发展、浸润和转移的关系。方法　采用免疫组织化学S P法检测 2 0例癌旁甲状腺组织 ,2 4例甲状腺腺瘤和 64例甲状腺癌的石蜡标本CD44V6 表达水平。结果　CD44V6 在甲状腺腺癌的表达率 ( 92 19%)显著高于甲状腺腺瘤者 ( 5 8 3 3 %,P <0 0 1) ,癌旁甲状腺组织未见表达。甲状腺中不同组织来源的滤泡细胞癌和髓样癌的CD44V6 表达差异具有显著性 ,总阳性率分别为 96 5 5 %及 5 0 0 %(P <0 0 1)。但CD44V6 表达水平在乳头状腺癌和滤泡型腺癌间差别无显著性 (P >0 0 5 )。同时发现 2例未分化癌CD44V6 表达均呈强阳性。CD44V6 的表达水平与甲状腺癌的包膜浸润和淋巴结转移有关 ,CD44V6 表达水平在包膜浸润组和未浸润组之间 ,在淋巴结转移组和非转移组之间差别有显著性 (P <0 0 1)。CD44V6 表达与患者年龄、性别、肿瘤的大小无关 (P >0 0 5 )。结论　CD44V6 的表达与甲状腺肿瘤的分化和浸润、转移显著相关 ,检测CD44V6 有助于甲状腺癌的诊断、判断预后并可能为甲状腺癌的手术和术后综合治疗决策提供新的分子生物学指标。     

CD44 expression in benign and malignant colorectal polyps

PURPOSE: This retrospective study was undertaken to evaluate immunohistochemically the expression of CD44 standard protein and CD44v5 and CD44v6 isoforms in colorectal adenomas and early invasive cancers developing within adenomas as possible markers characterizing colorectal polyps with a more aggressive biologic potential. METHODS: Archival tissues of 81 consecutive locally resected colorectal polyps, comprising 57 colorectal adenomas and 24 carcinomas-in-adenomas, were stained immunohistochemically with the use of commercially available mouse monoclonal antibodies: SFF-2 for CD44 standard protein, VFF-8 for CD44v5, and VFF-7 for CD44v6. RESULTS: Sixtythree percent of the colorectal polyps were positive for CD44 standard protein, 59 percent were positive for CD44v5, and 27 percent were positive for CD44v6. Ninetythree percent of the low-grade adenomas were CD44 standard protein-positive, in contrast to 50 percent of the high-grade adenomas and only 42 percent of the carcinomas-in-adenomas (Kendall's Tau =–0.42;P<0.0001). CD44v6 expression was more frequently found in early invasive cancers (54 percent) than in high-grade adenomas (25 percent) and low-grade adenomas (7 percent). This difference also was statistically significant (Kendall's Tau-b =0.39;P=0.00003). Surprisingly, a downregulation of CD44 standard protein expression was observed in the adenoma tissue adjacent to carcinomas (62 percent) and areas with high-grade atypia (71 percent), compared with low-grade adenomas (93 percent; Kendall's Tau-b =–0.28;P=0.004). CONCLUSIONS: Our data suggest that CD44 standard protein and CD44 isoform v6 expression differs considerably in benign and malignant colorectal polyps. Clinical studies with larger patient groups could clarify the prognostic potential of CD44 further     

骨桥蛋白和CD44v6在肝癌中的表达及意义

骨桥蛋白(osteopontin，OPN)是一种分泌型钙结合磷酸化糖蛋白，其中含有特异的与细胞黏附有关的RGD(Arg-Gly-Asp)序列，通过与其受体整合素、CD44等结合来促进细胞的趋化、黏附和迁移，从而介导肿瘤细胞的侵袭转移，在肿瘤的复发与转移中起到重要作用。OPN过表达与肝癌的复发和转移有关，并认为是早期预测肿瘤复发的一个指标。现对OPN和CD44v6在肝癌中的表达进行研究，以了解其临床意义。     

结直肠癌组织中CD44V3,v6蛋白的表达意义

目的研究CD44v3,v6蛋白在结直肠癌组织中的表达及其预后意义.方法应用EnvisionTM免疫组化法,回顾性分析121例结直肠癌石蜡组织CD44v3,v6的表达.患者中位随访时间为67.77mo.结果CD44v3,v6在结直肠癌中的阳性率分别为60.3%和57.9%.CD44v3的阳性表达与患者肿瘤部位,淋巴结转移状况、远处转移与否、临床分期密切相关(P＜0.05,Spearman等级相关检验).CD44v6的阳性表达与患者性别、淋巴结转移状况、远处转移与否、临床分期密切相关(P＜0.05,Spearman等级相关检验).Kaplan-Meier生存曲线,Log-rank检验单因素生存分析结果显示,CD44v3阴性、阳性患者的五年生存率分别为81.25%,60.27%,两者之间存在显著性差异(P=0.035);CD44v6阴性、阳性患者的5 a生存率分别为80.39%,60.00%,两者之间亦存在显著性差异(P=0.0299).Cox模型多因素生存分析结果显示,CD44v3表达是影响结直肠癌预后的独立因素.结论CD44v3,v6蛋白与结直肠癌转移、预后相关,CD44v3是影响结直肠癌预后的独立因素.