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 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.     

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。     

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.     

CD44v17在胃癌组织中的表达及其与临床生物学特性之间的关系

目的 探讨一种新的CD44变异体（CD44v17）在胃癌组织中的表达及其与临床生物学特性之间的关系.方法根据本实验室在MCF-7／Adr中新发现的1种CD44剪切拼接变异体CD44v17设计特异性引物,应用SYBR Green I荧光染料,采用实时PCR法检测87例胃癌组织及相应癌旁组织CD44v17 Mrna的表达,根据标准曲线计算CD44v17mRNA的表达量,分析CD44v17mRNA表达与胃癌临床生物学特性之间的关系.结果胃癌组织CD44v17 Mrna表达明显高于相应癌旁正常组织（P〈0.05）;肿瘤〉5 cm组CD44v17 Mrna表达与肿瘤≤5 cm组表达比较差异无显著性（P〉0.05）;未分化腺癌组表达明显高于乳头状腺癌及管状腺癌组（P〈0.05）,乳头状腺癌组CD44v17 Mrna表达与管状腺癌组比较差异无显著性（P〉0.05）;肿瘤累及浆膜及浆膜外组CD44v17 Mrna表达显著高于侵及黏膜、黏膜下层及肌层组（P〈0.05）,而肿瘤侵及黏膜及黏膜下层组的CD44v17 Mrna表达与侵犯肌层组表达比较差异无显著性（P〉0.05）.淋巴结转移组CD44v17 Mrna表达明显高于淋巴结无转移组（P〈0.05）;有肝脏转移组CD44v17 Mrna表达显著高于无肝脏转移组（P〈0.05）.结论CD44v17 Mrna在胃癌组织中高表达,可能与胃癌的侵袭、转移及预后有关.     

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．     

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.     

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。     

CD44v6和MMP-9在胎盘原位滋养细胞肿瘤中的表达及相关性

目的探讨CD44v6和基质金属酶-9（MMP-9）在胎盘原位滋养细胞肿瘤（PSTT）中的表达及相关性。方法采用SABC免疫组化法检测30例正常绒毛、15例PSTT的CD44v6和MMP-9表达情况。结果CD44v6在正常胎盘绒毛、良性PSTT、恶性PSTT的阳性表达率分别是3．3％、30．3％、100％,组间比较差异有统计学意义（P〈0．05）;而MMP-9的阳性表达率分别为6．7％、38．5％、100％,组间比较差异有统计学意义（P〈0．05）。结论CD44v6和MMP-9的过表达促进PSTT的浸润转移,二者具有正协同作用,联合检测CD44v6和MMP-9蛋白可作为PSTT的浸润转移及评价预后生物学指标。     

E-cad、CD_(44)v6基因表达与非小细胞肺癌淋巴转移的关系

目的探讨细胞粘附分子E-cad和CD44v6与非小细胞肺癌(non-small cell lung cancer,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E-cad和CD44v6基因蛋白的表达水平。结果E-cad在有无淋巴结转移组的正常表达率分别为21.1%和48.1%,两组比较差异有显著性(P0.05)。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(P0.05)。结论E-cad异常表达和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,且它们的作用具有协同性,它们的检测有助于判断NSCLC的淋巴结转移。     

肝细胞癌CD44v6和p16基因蛋白的表达及其意义

目的探讨CD44v6和p16基因蛋白表达与肝细胞癌(HCC)转移和预后的关系。方法应用免疫组织化学方法,检测分析110例HCC组织中CD44v6及p116蛋白表达,结合随访资料分析。结果在HCC中,CD44v6和p16阳性表达率分别为42.7%和34.5%。CD44v6阳性表达的HCC转移率高(P<0.05),分化程度和患者>5年生存率低(P<0.05);p16阳性表达的HCC转移率低(P<0.05),分化程度和患者>5年生存率高(P<0.05)。CD44v6与p16表达呈负相关(r=-0.59,P<0.005)。结论CD44v6和p16表达与HCC转移和患者生存期密切相关,检测CD44v6和p16蛋白的表达可作为判断HCC预后的参考指标。     

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。     

全直肠系膜切除术直肠系膜CD44v6检测47例

目的:通过检测CD44v6在的直肠癌及直肠系膜内的表达,从分子水平证明全直肠系膜切除术治疗直肠癌的科学性.方法:行全直肠系膜切除术的直肠癌患者47例于直肠癌组织、直肠系膜(距肿瘤下缘2cm)、直肠系膜远端切缘(距肿瘤下缘5cm)取病理标本,采用免疫组化SP法对标本进行CD44v6检测.结果:直肠癌组织中CD44v6高度表达,正常直肠系膜组织中CD44v6的阳性表达率(0/20)与直肠系膜(距肿瘤下缘2cm)的CD44v6的阳性表达率(15/47)存在显著差异(P<0.01),而与直肠系膜远端切缘(4/47)无差异(P>0.05).同时发现直肠癌中CD44v6的阳性表达率与肿瘤的淋巴转移(有vs无:88.5%vs61.9%,P<0.05)和临床分期(DukesC-DvsA-B:88.5%vs61.9%,P<0.05)有关.结论:对直肠癌组织进行CD44v6蛋白的检测,有助于评估直肠系膜局部病变程度;肿瘤远端直肠系膜切除长度至少比肿瘤平面多5cm.     

胆囊肿瘤组织中CD44v6和C-erbB-2的表达及相关性研究

研究CD4 4v6和C -erbB - 2癌基因蛋白产物在胆囊癌组织中的表达与组织类型、病理分级和转移的关系 ,并探讨CD4 4v6与癌基因蛋白表达的相关性。应用催化信号放大免疫组织化学方法 ,检测 5 0例胆囊腺癌、2 0例胆囊腺瘤和 10例慢性胆囊炎组织中CD4 4v6和C -erbB - 2表达。结果显示 ,在胆囊癌中CD4 4v6和C -erbB - 2阳性表达率分别为 82 0 %和 6 6 0 %。两者表达阳性率在胆囊癌中均明显高于胆囊腺瘤 (P <0 0 5 ) ,并与胆囊癌的组织类型、病理分级和转移密切相关 (P <0 0 5 )。CD4 4v6表达与C -erbB - 2表达呈明显相关联 (P <0 0 5 )。CD4 4v6和C -erbB - 2均是胆囊癌高度恶性和预后不良的重要指标。胆囊癌CD4 4v6表达与C -erbB - 2蛋白表达具有相互协同作用的可能     

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

ＩＮＴＲＯＤＵＣＴＩＯＮＣＤ４４ｉｓａｃｅｌｓｕｒｆａｃｅｔｒａｎｓｍｅｍｂｒａｎｅｇｌｙｃｏｐｒｏｔｅｉｎ．Ａｓａｋｉｎｄｏｆａｄｈｅｓｉｖｅｍｏｌｅｃｕｌｅ,ｉｔｐａｒｔｉｃｉｐａｔｅｓｉｎｃｅｌｃｅｌａｎｄｃｅｌｍａｔｒｉｘａｄｈｅｓｉｏｎ...     

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。     

Significance of immunohistochemical over-expression of CD44v6 as an indicator of malignant potential in esophageal squamous cell carcinoma

Purpose The aim of the current study was to find out a clinicopathologic significance of CD44v6 over-expression in esophageal squamous cell carcinoma (ESCC), which has not been elucidated fully.Methods Immunohistochemical expression of CD44v6 was examined for 81 ESCCs. Correlation of CD44 over-expression with the clinicopathologic features were investigated.Results Thirty-eight ESCCs (46.9%) had over-expression of CD44v6. The proportions of the incidence of lymph node metastasis (P=0.039), lymphatic permeation (P=0.003), and blood vessel invasion (P=0.037) in ESCCs with over-expression of CD44v6 were significantly higher than those in ESCCs without over-expression of CD44v6. The stage of the tumor in ESCCs with over-expression of CD44v6 was significantly more advanced (P=0.045). Survival rates of patients with ESCC with over-expression of CD44v6 were significantly worse (P=0.0005). Moreover, CD44v6 over-expression (P=0.048) as well as blood vessel invasion (P=0.014) and stage of the tumor (P=0.010) were factors independently associated with the unfavorable prognosis of the patients with ESCC.Conclusions Over-expression of CD44v6 can be an indicator of the malignant potential of ESCC.