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。     

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。     

喉癌组织中CD44v5、CD44v6蛋白的表达变化及意义

目的观察喉癌组织中细胞黏附分子CD44v5、CD44v6的表达变化,并探讨其临床意义。方法分别采用免疫组化SP法检测78例喉癌(观察组)及14例癌旁正常组织(对照组)中的CD44v5、CD44v6蛋白。结果观察组CD44v5、CD44v6蛋白阳性52、55例,对照组分别为4、0例;两组比较,P均<0.05。CD44v5、CD44v6蛋白表达与喉癌的TNM分期、组织分化程度及淋巴结转移有关(P均<0.05)。结论喉癌组织中CD44v5、CD44v6蛋白表达增加,两者可作为喉癌转移及预后评估的生物学指标。     

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.     

肝癌组织骨桥蛋白及CD44v6的表达与肝癌肝移植术患者预后的意义研究

目的研究骨桥蛋白(OPN)、CD44v6预测肝细胞癌肝移植患者预后效能,为寻求新的受体选择标准提供理论依据。方法收集2002年8月至2006年7月期间在西安交通大学医学院第一附属医院行经典原位肝移植术,且病理确诊为肝细胞癌的病例共30例。应用组化染色法,检测OPN、CD44v6的表达,进行统计分析。结果 30例肝细胞肝癌组织中OPN和CD44v6表达正相关。肝移植术后肿瘤复发转移与符合米兰标准情况显著负相关(P<0.01),与OPN、CD44v6的表达正相关(P<0.05)。在超出米兰标准的患者中,肿瘤复发与OPN、CD44v6阳性表达的相关性更强(P<0.01)。随访期内OPN或CD44v6染色阳性患者的生存率明显低于阴性患者(P=0.001),双阳性患者的生存率最低。对于超米兰标准的肝移植患者更为显著(P=0.004)。结论 OPN、CD44v6可以作为预测肝细胞癌肝移植患者预后的预测标签,联合检测OPN、CD44v6能够更好地反映超米兰标准的肝移植患者预后,检测OPN、CD44v6可以纳入受体选择标准。     

宫颈癌中KAI1/CD82与CD44v6的表达及相关性研究

目的 探讨肿瘤转移抑制基因KAI 1/CD82和细胞黏附分子CD44v6在宫颈癌组织中的表达及相关性.方法 应用免疫组织化学方法检测58例宫颈癌,16例CIN和10例正常宫颈组织中KA I1/CD82和CD44v6蛋白的表达.结果 KAI 1/CD82蛋白在正常宫颈组织中呈高表达,宫颈癌组织中呈低表达(P<0.05);其表达与患者年龄相关(P<0.01),但与临床分期、淋巴结转移、癌组织分化程度无关(P>0.05).CD44v6蛋白表达在宫颈正常组织中低表达,在宫颈鳞癌组织中高表达(P<0.05);与淋巴结转移、癌组织分化程度相关(P<0.01),但与患者年龄、临床分期无关(P>0.05).KAI 1/CD82与CD44v6呈负相关(r=-0.625 1,P<0.01).结论 KAI 1/CD82和CD44v6在宫颈癌的发生发展中起重要作用,有可能作为宫颈癌早期诊断和判断预后的重要指标.     

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及Ezrin在结肠癌中的表达及临床意义

目的 探讨CD44v6、Ezrin蛋白在结肠癌组织中的表达及临床意义.方法 应用免疫组化S-P法,检测47例结肠癌、20例正常结肠组织中CD44v6、Ezrin蛋白的表达.结果 CD44v6及Ezrin蛋白在结肠癌组织中的阳性率分别为68.09%(32/47)、74.47%(35/47),CD44v6及Ezrin蛋白在正常结肠组织阳性表达率为25.00%(5/20)、100.00%(20/20),有淋巴转移患者的Ezrin蛋白、CD44v6阳性率高于无淋巴转移患者(P<0.05);Ezrin蛋白在结肠癌组织中主要表达于胞浆,在正常肠组织主要表达于胞膜.结论 Ezrin蛋白、CD44v6的表达有助于综合判断结肠癌的恶性程度和转移潜能.Ezrin蛋白有望成为判断预后的新指标.     

原发性肝细胞癌中CD44v6和nm23H1基因的转录表达及临床意义

研究CD44v6 mRNA和nm23H1 mRNA表达与肝细胞癌（HCC）侵袭转移和预后的关系。应用原位杂交方法，检测分析HCC组织中CD44v6 mRNA和nm23H mRNA表达。99例HCC中，CD44v6 mRNA和nm23H1 mRNA表达阳性率分别为41．4％和76．8％。CD44v6mRNA表达与nm23H1mRNA表达呈负相关。CD44v6和nm23HmRNA表达均与HCC侵袭转移倾向和预后相关。检测CD44v6和nm23H1表达有可能成为HCC 侵袭转移和预后判断的病理生物学指标。     

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。     

黏附分子CD44的表达及其糖基化与肝癌转移的相关性

目的 探讨CD44S及其变异体CD44v分子的表达和其糖基化与肝癌细胞侵袭转移的关系. 方法 用免疫组织化学法、量子点、RT-PCR、Western blot、细胞免疫荧光染色、甲基化特异性聚合酶链反应等技术检测转移与非转移性肝癌组织、不同转移潜能人肝癌细胞株中CD44S及其变异体CD44v的定位与表达;并应用多重凝集素印迹法检测这些细胞株中CD44v6的糖基化差异.组间均数比较应用方差分析及t检验,多组间等级资料的比较采用Wilcoxon秩和检验,各组间率的比较采用x2检验.结果 免疫组织化学结果显示,CD44S蛋白定位以细胞质为主; CD44v3、CD44v4/5蛋白定位于细胞膜与细胞质;而CD44v6主要定位于细胞膜.组织芯片结果显示,相对于CD44S及其他CD44v,CD44v6在转移组的表达水平高于非转移组(阳性率为75％与46％),差异具有统计学意义(x2=8.828,P＜0.05);量子点检测(t=2.392,P＜0.05)与血清学检测(t=2.56,P＜0.05)也证实这一结果.Western blot结果显示,CD44v6的表达与肝癌细胞转移潜能呈正相关.此外,在MHCC97L、MHCC97H肝癌细胞中CD44v6基因启动子发生不完全甲基化,而在Hep3B细胞中则发生完全甲基化.而且,相对于Hep3B细胞,MHCC97L及MHCC97H细胞中CD44v6蛋白对朝鲜槐凝集素、黑接骨木凝集素及麦胚凝激素的亲和力较高. 结论 在CD44S及其变异体CD44v中,CD44v6蛋白的高表达与肝癌转移潜能的增强呈正相关;其高表达可能与基因启动子低甲基化有关.此外,CD44v6蛋白唾液酸寡糖链的增加可能与肝癌细胞转移潜能增高有关.     

VEGF和CD44v6过表达与乳腺癌浸润转移的关系

目的检测血管内皮生长因子(VEGF)和转移相关黏附分子44v6(CD44v6)在乳腺癌中的表达情况,探讨两者与淋巴结转移的关系。方法采用免疫组化SP法检测92例乳腺浸润性癌中VEGF、CD44v6的表达情况。结果 VEGF在正常乳腺组织和乳腺癌中的阳性表达率分别为6.7%(3/45)和90.2%(83/92),且VEGF在淋巴结转移组中的阳性表达率(53/55)明显高于无淋巴结转移组(P<0.05)。CD44v6在正常乳腺组织及乳腺癌中的阳性表达率分别为8.9%(4/45)和85.9%(79/92),而且CD44v6在淋巴结转移组中的阳性表达率(51/55)明显高于无淋巴结转移组(P<0.05)。VEGF和CD44v6表达呈正相关关系(r=0.497,P<0.05)。结论 VEGF、CD44v6在乳腺癌组织中高表达,且均与淋巴结转移有关(P<0.05),两者可能在乳腺癌的远处转移中起协同作用。     

Expression of human chorionic gonadotropin, CD44v6 and CD44v4/5 in esophageal squamous cell carcinoma

AIM: To study the relationship between the expression of human chorionic gonadotropin (HCG), CD44v6, CD44v4/5 and the infiltration, metastasis of esophageal squamous cell carcinoma. METHODS: By labeled streptavidin-biotin technique, the expressions of HCG, CD44v6, and CD44v4/5 in 42 patients with esophageal squamous cell carcinoma were examined. RESULTS: The positive rate of HCG expression in patients with lymph node metastasis was 85.71% (18/21), higher than that (57.14%, 12/21) in those without lymph node metastasis (P<0.05). The positive rate of CD44v6 expression was 71.43% (15/21) in lymph node metastasis group, and 38.09% (8/21) in non-metastasis group; there was a significant difference between the two groups (P<0.05). The positive rate of CD44v4/5 expression was 76.19% (16/21) in lymph node metastasis group, and 42.86% (9/21) in non-metastasis group; there was also a significant difference between them (P<0.05). From grade Ⅰ to grade Ⅲ in differentiation, the positive rate of HCG expression was 84.62% (11/13), 70.59% (12/17) and 58.33% (7/12), respectively; there was no significant difference among them (P<0.05). The positive rate of CD44v6 expression in grades Ⅰ-Ⅲ of cancer tissues was 76.92% (10/13), 52.94% (9/17), and 33.33% (4/12) respectively; there was no significant difference among them. The positive rate of CD44v4/5 expression in grades Ⅰ-Ⅲ of cancer tissues was 69.23% (9/13), 64.71% (11/17), and 41.67% (5/12) respectively; there was no significant difference among the three groups. There was no correlation between the positive rates of HCG and CD44v6, CD44v4/5 expression. Cancer cells in carcinomatous emboli and those infiltrating into vascular wall strongly expressed HCG, CD44v6, and CD44v4/5. CONCLUSION: Expression of HCG, CD44v6, and CD44v4/5 in esophageal squamous cell carcinoma is related to its infiltration and metastasis. HCG, CD44v6, and CD44v4/5 have different effects on the infiltration and metastasis of esophageal squamous cell carcinoma.     

Relationship between expression of CD44v6 and nm23-H1 and tumor invasion and metastasis in hepatocellular carcinoma

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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.     

Expression of two CD44 variant proteins (v3 and v6 ) in human colorectalcarcinoma and its relevance for prognosis

AIM To evaluate the expression of CD44v3 and v6 protein in colorectal carcinoma and its prognosticsignificance.METHODS One hundred and twenty-one cases of formalin-fixed paraffin-embedded colorectal carcinomaspecimens were retrospectively analyzed using EnvisionTM immunohistochemical method with the monoclonalantibody CD44v3 and v6. The median follow-up time was 67.77 months and the prognostic value of theCD44v3 and CD44v6 was assessed using univariate and multivariate survival analysis.RESULTS The positive rates of CD44v3 and v6 protein were 60.3% and 57.9%, respectively. There wassignificant correlation between CD44v3 immunoreactivity and tumor location, lymph node metastasis, distantmetastasis and Duke's stage (P< 0.05, Spearman correlation test). Significant correlation between CD44v6immunoreactivity and patients' gender, lymph node metastasis, distant metastasis, Duke's stage was alsonoticed (P < 0.05, Spearman correlation test). The 5-year survival rates were 81.25% and 60.27% inCD44v3 negative and positive cases, respectively. As CD44v6, the 5-year survival rates were 80.39% and60.00% in CD44v6 negative and positive cases, respectively; these differences between the two groups ofpatients were significant (P<0.05, Log-rank test). In multivariate analysis using the Cox regression model,CD44v3 expression emerges as an independent prognostic indicator.CONCLUSION CD44v3 and v6 might play some important roles in metastasis of colorectal carcinoma, andCD44v3 expression might be a new useful independent prognostic marker of colorectal carcinoma.     

Expression of adhesion molecules in hepatic metastases of colorectal carcinoma: Relationship to primary tumours and prognosis after hepatic resection

BACKGROUND: Adhesion molecules are closely involved in the development and growth of metastatic tumours. METHODS: We examined the expression of two adhesion molecules in liver metastatic tumours originating from colorectal carcinomas and correlated the expression of E-cadherin (EC) and CD44 variant exon 6 (v6) in these tumours with prognosis after hepatic resection. We examined 39 primary colorectal and 44 liver metastatic tumours obtained from 39 patients and 30 non-metastatic colorectal carcinomas as controls. The expression of EC in primary colorectal carcinomas of the metastasis group was significantly lower than in the non-metastasis group (P < 0.05). The expression of EC was low in metastatic liver tumours. RESULTS: The expression of CD44v6 in primary colorectal carcinomas of the metastasis group was significantly higher than in the non-metastasis group (P < 0.01). Expression of CD44v6 was high in metastatic liver tumours. However, there was no correlation between the expression of EC and CD44v6 or between each of these molecules and clinicopathological features of primary and metastatic tumours. Negative expression of EC and CD44v6 was a poor prognostic factor for survival after hepatic resection. CONCLUSIONS: Our results indicate that the lack of expression of EC and CD44v6 in liver metastases of colorectal cancer is associated with poor survival after surgery.