c-erbB-2、CD44v6的表达与非小细胞肺癌淋巴转移的关系

目的探讨癌基因c-erbB-2和细胞黏附分子CD44v6与非小细胞肺癌(NSCLC)淋巴结转移的关系。方法应用免疫组织化学SABC法检测65例原发性NSCLC组织中c-erbB-2和CD44v6基因蛋白的表达水平。结果c-erbB-2在有无淋巴结转移组的阳性表达率分别为73.7%和48.1%,两组比较差异有显著性(P<0.05)。CD44v6在有无淋巴结转移组的阳性表达率分别为78.9%和55.6%,两组比较差异有显著性(P<0.05)。在有淋巴结转移的NSCLC中,c-erbB-2和CD44v6基因蛋白的表达呈显著相关关系。结论c-erbB-2阳性表达和CD44v6阳性表达可能均在NSCLC的淋巴结转移中起重要的促进作用,且二者的作用具有协同性。对c-erbB-2和CD44v6的检测有助于判断NSCLC的淋巴结转移。     

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。     

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.     

CD44s和CD44v6在肺癌组织中的表达及意义

采用免疫组化法检测107例肺癌组织中标准型CD44（CD44s）和变异型CD44（CD44v）6的表达,结果，17例小细胞肺癌（SCLC）中，CD44v6和CD44s均无表达;非小细胞肺癌（NSCLC）中，CD44v6和CD44s在鳞癌中的阳性表达率（81．0％和83．3％）均高于腺癌（39．6％和54．2％），P均〈0．05;无淋巴结转移的NSCLC中，CD44v6阳性表达率（34．0％）低于CD44s（78．0％）。P〈0．05；有淋巴结转移的NSCLC中．CD44v6阳性表达率（90．0％）高于CD44s（55．0％），P〈0．05。NSCLC的CD44v6和CD44s表达与其病理类型、临床分期、肿瘤分级及淋巴结转移均有关（P均〈0．05）。认为CD44v6和CD44s可以作为鉴别SCLC与NSCLC及判断肺癌病理类型、临床分期、肿瘤分级及淋巴结转移的参考指标。     

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.     

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。     

食管癌中淋巴结转移与VEGF,CD44v6,MMP-2水平变化的相关性

目的研究食管癌患者的癌组织发生淋巴结转移与病变组织中血管内皮生长因子(vascular endothelial growth factor,VEGF),细胞黏附分子(cell adhesion molecule,CAM)变异体v6(CD44v6)及基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)的水平的关系.方法 2016-03/2017-09经浙江省长兴县人民医院确诊为食管癌的患者纳入104例,根据良恶性分为食管癌组83例和良性组21例,比较两组患者中VEGF,CD44v6及MMP-2三者的阳性水平,并对不同表达食管癌组织患者的淋巴结是否发生转移进行分析.结果食管癌组VEGF,CD44v6及MMP-2阳性表达率分别为77.11%,73.49%,59.04%,良性组织的阳性表达率分别为14.29%,23.81%,14.29%,三者在食管癌组中的阳性表达情况显著高于良性组,差异具有统计学意义P0.05;VEGF,CD44v6及MMP-2在发生淋巴结转移的食管癌患者中阳性率依次为85.48%,82.26%,66.13%,而未发生淋巴结转移的患者粘膜组织中的阳性率为52.38%,52.38%,38.10%,发生淋巴结转移的食管癌组织标本中三者阳性表达率显著高于未发生转移组织,差异显著P0.05.结论 EGF,CD44v6及MMP-2在食管癌患者癌变组织中的水平与其淋巴结是否发生转移具有一定关系,对食管癌患者的早期正确诊断,治疗以及预后效果评估具有重要意义.     

Muc-1 mRNA和CD44 mRNA在非小细胞肺癌组织中的表达及与预后的关系

目的 探讨Muc-1 mRNA和CD44 mRNA在非小细胞肺癌(NSCLC)组织中的表达情况与淋巴结转移的相关性及其与预后的关系.方法 应用RT-PCR方法检测36例NSCLC组织中和10例正常肺组织中Muc-1 mRNA和CD44 mRNA的表达情况.结果 ① 36例NSCLC组织中有19例Muc-1 mRNA阳性表达,阳性表达率为52.7%;21例CD44 mRNA表达,阳性表达率为58.3%.②Muc-1 mRNA在NSCLC组织中的阳性表达与患者的年龄、性别、组织学类型、TNM分期、肿瘤大小无关(P＞0.05),与淋巴结转移有关(χ2 =10.166,P＜0.05);CD44 mRNA在NSCLC组织中的阳性表达与患者的年龄、性别、组织学类型、TNM分期、肿瘤大小无关(P＞0.05),与淋巴结转移有关(χ2=8.371,P＜0.05).③Muc-1 mRNA和 CD44 mRNA阳性表达与NSCLC患者的预后有关(P＜0.05).④Muc-1 mRNA和CD44 mRNA在NSCLC组织中表达成正相关(r=0.442,P＜0.05).结论 Muc-1 mRNA和 CD44 mRNA阳性表达的NSCLC患者淋巴结转移率高,对NSCLC患者预后判断具有一定的指导作用.     

胃癌患者c-erB-2和CD44V6基因蛋白的表达及其与淋巴转移的关系

目的 探讨癌基因c-erB-2和细胞黏附分子(CAMs)CD44V6基因蛋白在胃癌中的表达及其与淋巴转移的关系.方法 应用免疫组织化学SABC法检测67例胃癌组织中c-erB-2、CD44V6基因蛋白的表达水平.结果 c-erB-2在有淋巴转移组和无淋巴转移组的阳性表达率分别为79.5%(31/39)和50.0%(14/28),两组比较差异有显著性(P＜0.05).CD44V6在有淋巴转移组和无淋巴转移组的阳性表达率分别为76.9%(30/39)和60.7%(17/28),两组比较差异有显著性(P＜0.05).在有淋巴转移的胃癌中c-erB-2和CD44V6表达呈显著相关关系.结论 c-erB-2和CD44V6基因蛋白的表达可能在胃癌的转移过程中具有重要的促进作用,且二者具有协同性.检测c-erB-2和CD44V6有助于判断胃癌的淋巴转移及其预后.     

老年大肠癌患者外周血CD44v5、CD44v6表达及化疗对其影响

目的　研究老年大肠癌患者外周血CD44v5、CD44v6表达水平与血行转移的关系及化疗对其影响。方法　应用流式细胞仪检测 49例老年大肠癌患者手术前外周血CD44变异体 (CD44v5、CD44v6)表达水平 ,与健康老年人及非老年大肠癌患者进行对照 ,并在应用化疗后观察黏附分子表达水平的变化。结果　老年大肠癌组外周血CD44v5、CD44v6的表达水平分别为 1 0 71± 5 44、1 4 62± 6 34 ,明显高于健康对照组 (P <0 0 1 ) ,与非老年大肠癌组比较无显著性差异 (P >0 0 5)。CD44v5、CD44v6的表达水平与老年大肠癌患者肿瘤大小、肿瘤浸润深度及淋巴结转移相关 ,老年大肠癌组肿瘤≥ 5cm、肿瘤浸润深度≥深肌层、淋巴结转移阳性患者外周血CD44v5、CD44v6的表达水平分别高于肿瘤 <5cm、肿瘤浸润深度 <深肌层、淋巴结转移阴性患者 (P <0 0 1、P <0 0 5、P <0 0 1 )。老年大肠癌患者化疗后外周血CD44v5、CD44v6表达水平较化疗前明显下降 (P<0 0 1 )。结论　黏附分子具有介导老年人大肠癌细胞血行转移的作用 ,化疗可降低老年大肠癌患者外周血CD44v5、CD44v6的表达水平 ,具有抗黏附和肿瘤转移作用     

CD44在肺癌中表达的临床研究

目的观察标准型白细胞分化抗原（ＣＤ４４ｓ）及变异型白细胞分化抗原（ＣＤ４４ｖ６）在肺癌中的表达情况及同肺癌淋巴结转移的关系。方法以ＳＰ法对９６例原发性肺癌及１２例转移淋巴结行免疫组化研究。结果在小细胞肺癌（ＳＣＬＣ）中，未见ＣＤ４４表达；而在非小细胞肺癌（ＮＳＣＬＣ）中，鳞癌（ＳＣＣ）的ＣＤ４４表达明显高于腺癌（ＡＤＣ）（Ｐ＜０．０１）；在１２例转移淋巴结中，１０例（８３％）表达ＣＤ４４ｖ６阳性；同未发生淋巴结转移的原发性肺癌（５１％）相比，发生转移的原发性肺癌中ＣＤ４４ｖ６表达明显增多（９１％，χ２＝１４．９２，Ｐ＜０．０１）；ＣＤ４４ｓ及ＣＤ４４ｖ６表达同肺癌分化程度无关；按ＴＮＭ分期，Ⅲ＋Ⅳ期中ＣＤ４４ｖ６表达显著高于Ⅰ＋Ⅱ期肺癌（χ２＝６．０５，Ｐ＜０．０５）。结论ＣＤ４４大部分表达于ＮＳＣＬＣ中，且主要在ＳＣＣ中；ＣＤ４４ｖ６阳性可能预示ＮＳＣＬＣ发生淋巴结转移的倾向，并可能对肺癌临床分期起到一定作用     

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.     

CD44 and its v6 spliced variant in lung carcinomas: relation to NCAM, CEA, EMA and UP1 and prognostic significance

CD44 is a polymorphic family of cell surface glycoproteins that was recently reported to have important role in cell adhesion and migration as well as modulation of cell-matrix interactions. Thus, expression of CD44 has been proposed to be associated with malignant behavior of tumors like invasive growth and formation of metastasis. The expression of CD44s and its v6 isoform (CD44v6) was determined immunohistochemically in 106 lung tumors of various histophenotypes, degrees of differentiation, and clinical stages. The results were compared with the expression of NCAM, CEA, EMA and UP1 and with clinicopathological parameters including patients' survival. CD44s was expressed in all histophenotypes of non-small cell lung carcinomas (NSCLC) with tendency being squamous cell lung carcinoma (SqCC) > bronchioloalveolar adenocarcinoma (BAC) > conventional adenocarcinoma (ConAC) (91, 66.7 and 38.9%, respectively). Almost identical distribution of positivity revealed CD44v6 in all three subgroups of NSCLC mentioned above (91, 66.7 and 36.1%, respectively). In the subgroup of neuroendocrine tumors, CD44s and CD44v6 were restrictedly expressed in small cell lung carcinomas (2/14 tumors), while all 3 typical carcinoids were strongly positive for these markers. Expression of NCAM and CEA was significantly higher in adenocarcinoma subgroup than those in SqCC subgroup (45.7 and 75% vs. 14.8 and 39%, respectively). NCAM expression was also significantly different in BACs and in ConACs (69.2 vs. 36.4%, p < 0.05). The expression of CD44 was related to the differentiation of SqCC. The carcinomas with keratinization were CD44 positive. Adenocarcinomas producing mucin were CD44 negative. The expression of CD44, NCAM, CEA, EMA and UP1 did not correlate with lymph node metastasis and disease stage. CD44V6 was the only marker that its expression was closely related to patients' survival. The absence CD44v6 but not CD44s in NSCLC group was associated with significantly longer survival of patients compared to patients with CD44v6 positive tumors. This difference was even higher in tumors negative for CD44v6 and simultaneously NCAM and/or CEA positive. The data of this study suggest that CD44v6 might be an independent prognostic factor in NSCLC. Moreover, our data give another evidence of diverse role of CD44 in the differentiation and progression of non-small cell lung carcinomas and neuroendocrine carcinomas of the lung.     

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。     

钙黏蛋白和基质金属蛋白酶-2在非小细胞肺癌中的表达及其与血管生成拟态的关系

目的 探讨在非小细胞肺癌( NSCLC)中E-钙黏蛋白(E-cad)和基质金属蛋白酶-2(MMP-2)的表达及其与血管生成拟态(VM)的关系.方法 采用免疫组化ElivisionTM plus法和特殊组织化学法检测160例NSCLC和20例正常肺组织中E-cad、MMP-2的表达水平和VM情况.结果 在正常肺组织中E-cad、MMP-2的表达率和VM分别为100％、25.0％和0％,在NSCLC组织中分别为45.6％、66.3％和36.9％,差异显著(P＜0.01);其水平与肿瘤细胞分化程度、淋巴结转移、临床分期和术后生存期有关(均P＜0.01);E-cad的表达水平与MMP-2的表达水平及VM呈负相关,MMP-2的表达水平与VM呈正相关(均P＜0.01).Kaplan-Meier生存分析表明MMP-2的过表达和VM均与患者的生存率有关,阳性患者生存率明显低于阴性者(P＜0.01);而E-cad阳性表达的患者生存率明显高于阴性者(P＜0.01).多因素分析:PTNM分期、淋巴结转移、E-cad和MMP-2的表达以及VM是影响NSCLC根治术后患者预后的独立因素(P＜0.01).结论 E-cad、MMP-2在NSCLC组织中的表达水平以及VM与肿瘤的分化程度、转移和预后等均有关,E-cad、MMP-2和VM联合检测对NSCLC的进展及预后判断有重要意义.     

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.     

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.