非小细胞肺癌中CD44v6的表达

目的　探讨CD4 4v6表达与非小细胞肺癌临床病理特征之间的关系。方法　采用免疫组化S P法检测 132例非小细胞肺癌、6 6例淋巴结转移癌和 115例正常肺组织CD4 4v6表达的情况。结果　非小细胞肺癌CD4 4v6阳性表达率为4 8 4 8% ,高于正常肺组织 17 39%的阳性表达率。CD4 4v6阳性表达与淋巴结转移状况、TNM分期、肿瘤大小和组织学类型有相关性。非小细胞肺癌淋巴结转移组、TNMⅢ期患者、直径 >3cm的肿瘤和鳞癌CD4 4v6阳性表达率分别高于无淋巴结转移组、TNMⅠ期和Ⅱ期患者、直径≤ 3cm的肿瘤和腺癌。淋巴结转移癌CD4 4v6阳性表达率高于肺原发癌。CD4 4v6阳性表达与患者的性别、年龄和组织学分级无相关性。结论　CD4 4v6阳性表达预示非小细胞肺癌具有较强的侵袭和转移能力 ,可作为一项预测非小细胞肺癌转移潜能生物学指标。     

E-cadherin、β-catenin、CD44v6在乳腺癌中的表达

目的　探讨乳腺癌中E cadherin(E cad)、β catenin(β cat)、CD4 4v6蛋白表达。 方法　采用免疫组化S P法测定 4 8例乳腺癌中E cad、β cat、CD4 4v6蛋白的表达。 结果　E cad、β cat蛋白的表达强度 ,无淋巴结转移组高于有淋巴结转移组 (P <0 0 5 ) ,与肿瘤的大小、病理分级、组织学分类无关 ;在乳腺癌中随着E cad强度的增加 ,β cat阳性率亦呈上升趋势 (P <0 0 5 )。CD4 4v6蛋白的表达强度 ,有淋巴结转移组高于无淋巴结转移组 (P <0 0 5 ) ,与肿瘤的大小、病理分级、组织学分类无关。结论　E cad、β cat、CD4 4v6的表达可作为判断乳腺癌是否转移的可靠指标     

结直肠癌CD44V6、E-cadherin和VEGF的表达及其意义

目的：探讨结直肠癌CD44V6、E-cadherin和VEGF的表达及其临床意义。方法：应用免疫组化S－P法检测46例结直肠癌CD44V6、E-cadherin和VEGF的表达，并分析其与结直肠癌临床病理特征的关系。同时检测了23例淋巴结转移灶CD44V6、E-cadherin和VEGF的表达。结果：结直肠癌组织中CD44V6、E-cadherin和VEGF阳性表达率分别为50．0％、56．5％、和50．0％；原发灶CCD4V6和VEGF阳性表达率低于淋巴结转移灶（60．9％和56．％），而原发灶E-cadherin阳性表达率则高于淋巴结转移灶（43．5％）。结直肠癌CDV46和VEGF阳性表达与淋巴结转移，局部浸润深度和Dukes分期等有关。E-cadherin阳性表达与结直肠癌临床病理特征无关。结论：CD44V6和VEGF是结直肠癌发生与发展重要的促进因子，其过度表达与结直肠癌浸润转移，病理分期有关，可作为预测结直肠癌预后的生物学指标之一。     

非小细胞肺癌中Ezrin和CD44v6的表达及意义

目的 探讨非小细胞肺癌中Ezrin和CD44v6的表达及其与肺癌各种临床病理参数之间的关系.方法 采用免疫组化SP法检测55例非小细胞肺癌组织中Ezrin及CD44v6的表达.结果 Ezrin的表达程度与非小细胞肺癌的TNM分期(P=0.004)和淋巴结转移(P=0.003)密切相关; CD44v6的表达程度与非小细胞肺癌的TNM分期(P=0.012)和淋巴结转移(P=0.010)密切相关;Ezrin 和CD44v6两者在非小细胞肺癌组织中的表达呈正相关(r=0.568, P=0.000).结论 Ezrin和CD44v6与肺癌淋巴结转移和临床TNM分期密切相关,联合检测Ezrin和CD44v6有助于判断肺癌的预后.     

CD44v4在乳腺浸润性导管癌中的表达及 其与浸润转移的关系

目的 探讨CD44v4在浸润性乳腺导管癌中的表达及其与浸润转移的关系。方法 选取2011年1月~2018年3月我院收治的乳腺浸润性导管癌185例设为观察组,另选取同期收治的乳腺良性疾病患者60例设为对照组,采用免疫组化法检测两组CD44v4的表达情况,并比较观察组CD44v4表达及临床病理因素情况。结果 观察组CD44v4阳性表达率为60.54%,高于对照组的5.00%,差异有统计学意义（P＜0.05）。CD44v4表达在不同年龄、绝经前后月经状况、原发瘤大小间比较,差异无统计学意义（P＞0.05）;不同TNM分期、组织学分级、淋巴结转移患者的CD44v4表达比较,差异有统计学意义（P＜0.05）。结论 CD44v4蛋白在乳腺浸润性导管癌患者中为高表达,检测其表达可作为判断肿瘤预后的新指标。     

乳腺癌中OPN、CD44v6及CD10的表达及其临床意义

目的探讨骨桥蛋白(osteopontin,OPN)、CD44v6、CD10在乳腺癌及腺病中的表达,分析三者与乳腺癌临床病理特征及预后的相关性。方法采用免疫组化En Vision两步法检测OPN、CD44v6、CD10在浸润性癌非特指型(153例)、导管原位癌(40例)、腺病(28例)中的表达;采用χ2检验分析三者与乳腺癌临床病理特征的关系,多因素分析采用Cox回归模型,预后分析采用Kaplan-Meier法,组间差异比较采用Log-rank检验。结果在腺病、导管原位癌、浸润性癌非特指型中,OPN阳性率分别为7.1%、27.5%、56.2%,CD44v6阳性率分别为10.7%、40.0%、57.5%,CD10阳性率分别为3.5%、37.5%、55.6%。三者在腺病中的阳性率均低于乳腺癌,差异具有统计学意义(P=0.020、0.042、0.003)。浸润性癌非特指型组织中OPN、CD44v6和CD10的表达均与组织学分级、淋巴结转移相关,且OPN、CD44v6表达均与p TNM分期相关,CD44v6表达与PR状态相关(P均0.05);在导管原位癌中三者的表达与核分级相关,差异均有统计学意义(P均0.05);三者的表达与患者年龄、绝经状态、脉管浸润、Ki-67增殖指数、ER状态、HER-2状态均无关(P均0.05)。OPN、CD44v6和CD10在乳腺癌中的表达两两间均呈正相关(P均0.001)。多因素分析提示淋巴结转移、CD10阳性是浸润性癌非特指型患者的预后影响因素。生存分析显示在浸润性癌非特指型中,三者均阴性组患者的无病生存率(disease-free survival,DFS)、总生存率(overall survival,OS)均优于三者均阳性组,差异有统计学意义(P=0.010、0.007)。结论 OPN、CD44v6、CD10在乳腺癌中高表达,均与乳腺癌进展相关。联合检测OPN、CD44v6、CD10在乳腺癌中的表达,对于判断患者预后具有重要价值。     

CD44s和CD44v6在宫颈鳞癌中表达及其临床意义

目的：探讨宫颈鳞癌中CD44s和CD44v6的表达及其与临床病理资料的关系。方法：应用免疫组化EnVision两步法对31例宫颈鳞标本中CD44s和CD44v6蛋白表达并进行分析。结果：肿瘤原发灶中CD44s阳性表达率为61．3％（19／31）。CD44v6阳性表达率为93．5％（29／31）,CD44v6阳性率高于CD44s,CD44s阳性表达与临床分期,病理分级和分类无关（P＞0．05）,CD44v6阳性表达与肿瘤细胞分化程度无关,但与浸润程度及分期有关（P＜0．05）,结论：CD44v6基因蛋白与宫颈鳞癌的侵袭,转移相关,可作为预测肿瘤进展和预后的一种有用指标。     

食管癌组织中多药耐药相关蛋白和CD44v6的表达

目的　探讨多药耐药相关蛋白 (multidrugresistance associatedprotein ,MRP)和CD44v6在食管癌组织中表达的意义 ,以及两者之间的关系。方法　采用免疫组织化学S P法检测 74例食管癌组织中MRP和CD44v6的蛋白表达。结果　MRP和CD44v6在食管癌组织中的阳性表达率分别为 5 1 4 %和 83 8%,食管癌中MRP的表达与肿瘤的浸润深度和淋巴结转移呈正相关 (P <0 0 5 ) ,而与肿瘤的分化程度无关 (P >0 0 5 )。CD44v6在食管癌中的表达与肿瘤的浸润深度和淋巴结转移密切相关 (P <0 0 5 ) ,而与肿瘤的分化程度无关 (P >0 0 5 )。CD44v6在MRP阳性食管癌中的表达明显高于其在MRP阴性食管癌中的表达 (P <0 0 5 )。结论　肿瘤多药耐药可能与肿瘤转移有关 ,检测食管癌中MRP和CD44v6的表达可能反映肿瘤细胞的生物学行为。     

大肠癌中CCR7、L-selectin、CD44v6和MMP9表达及其与淋巴转移的关系

目的探讨CC趋化因子受体7(CCR7)、L-selectin、CD44v6和MMP9在大肠癌组织中的表达及其与大肠癌淋巴转移的关系。方法采用免疫组化PV 9000两步法检测104例大肠癌组织(大肠癌组)、55例癌旁正常组织(癌旁组)和34例转移灶组织(转移组)中CCR7和L-selectin、CD44v6和MMP9的表达。结果大肠癌组、转移组中CCR7、L-selectin、CD44v6和MMP9阳性率明显高于癌旁组(P<0.05),有淋巴结转移者明显高于无转移者(P<0.05);CCR7与L-selectin、MMP9表达呈正相关(P<0.05);CD44v6与L-selectin、MMP9表达相关;L-selectin与MMP9的表达呈正相关。结论 CCR7、L-selectin、CD44v6和MMP9在大肠癌中的表达与大肠癌的发生、淋巴转移有关,它们可能共同参与了大肠癌发生及淋巴结转移过程。     

CD44和CD44v6基因在胃腺癌组织中的表达及其意义

目的： 研究胃腺癌组织中ＣＤ４４ 的表达及其与淋巴结转移和预后的关系。方法： 应用免疫组化方法, 对１０５ 例胃腺癌组织中ＣＤ４４ 的表达进行了观察, 并对其中６２ 例患者做了随访。结果： ＣＤ４４ 和ＣＤ４４ｖ６ 基因的表达率分别为５４－３ ％ 和４８－６ ％ 。ＣＤ４４ｖ６ 在胃腺癌组织中的表达与癌细胞的分化、浸润深度, 以及临床分期和预后有关（Ｐ＜ ０－０５）, 而ＣＤ４４ 的表达则与上述临床病理指标无关。另外, 抗ＣＤ４４ 和抗ＣＤ４４ｖ６ 抗体的阳性反应, 与癌细胞的淋巴结转移有关（ＣＤ４４ｖ６, Ｐ＜ ０－０１ ; ＣＤ４４ , Ｐ＜ ０－０５） 。结论： ＣＤ４４ 的表达可用于胃癌患者的病情监测, 其中ＣＤ４４ｖ６ 有望作为判断预后的一个指标。     

上皮钙黏蛋白和CD44v6蛋白在青年胃腺癌组织中的表达及其临床意义

目的:探讨上皮钙黏蛋白(E-cad)与CD44v6蛋白在青年(≤35岁)胃癌组织中的表达及其与临床病理特征之间的关系.方法:收集68例青年(≤35岁)和68例老年(≥60岁)胃腺癌组织,用免疫组织化学EnVision法检测E-cad和CD44v6的表达.结果:远离癌组织的正常胃黏膜上皮几乎全部上皮细胞膜着色,即正常表达;而胃癌组织中E-cad呈异常表达,即细胞质着色或异质性着色.青年胃癌组织E-cad异常表达率和CD44v6阳性表达率分别为70.6%和76.5%,而老年胃癌组织E-cad异常表达率和CD44v6阳性表达率分别为42.6%和51.5%,两者比较差异有统计学意义.青年胃癌淋巴结癌转移组和无淋巴转移组E-cad异常表达率分别为63.6%和32.6%,差异有统计学意义;CD44v6淋巴结癌转移组阳性表达率为80.4%;无淋巴转移组阳性表达率63.6%,差异有统计学意义.青年胃癌组织中E-cad异常表达和CD44v6蛋白表达呈正相关.结论:E-cad蛋白异常表达及CD44v6蛋白高表达预示青年胃癌具有较强的侵袭转移能力,可作为预测青年胃癌转移潜能的生物学指标.     

CD44v6 expression in patients with stage II or stage III sporadic colorectal cancer is superior to CD44 expression for predicting progression

Background: Currently, it is difficult to predict the prognosis of patients exhibiting stage II or stage III colorectal cancer (CRC) and to identify those patients most likely to benefit from aggressive treatment. The current study was performed to examine the clinicopathological significance of CD44 and CD44v6 protein expression in these patients. Study design: We retrospectively investigated 187 consecutive patients who underwent surgery with curative intent for stage II to III CRC from 2007 to 2013 in the Beijing Civil Aviation Hospital. CD44 and CD44v6 protein expression levels were determined using immunohistochemistry and compared to the clinicopathological data. Results: Using immunohistochemical detection, CD44 expression was observed in 108 (57.75%) of the CRC patients; and its detection was significantly associated with greater invasion depth, lymph node metastasis, angiolymphatic invasion, and a more advanced pathological tumor-lymph node-metastasis (TNM) stage. CD44v6 expression was observed in 135 (72.19%) of the CRC patients; and its expression was significantly associated with a poorly differentiated histology, greater invasion depth, lymph node metastasis, angiolymphatic invasion, and a more advanced pathological TNM stage. Expression of CD44v6 was higher than that of CD44 in stage II and stage III sporadic CRC. Conclusion: CD44v6 is a more useful marker for predicting a poor prognosis in stage II and stage III sporadic CRC as compared to CD44.     

Systematic assessment of the prognostic impact of membranous CD44v6 protein expression in colorectal cancer

Aims:  To assess systematically the membranous expression of CD44v6 in colorectal cancer by immunohistochemistry to determine its prognostic impact, the differential expression between primary and metastatic tumours and expression differences between the tumour centre and invasive front.
Methods and results:  Immunohistochemistry was performed for CD44v6 on two tissue microarrays. The first included 1279 colorectal tumours with full clinicopathological data. The second consisted of 50 matched primary and metastatic tumours sampled from the tumour centre and the invasive margin. A scoring system was tested by multiple observers. Receiver–operating characteristic curve analysis was used for cut-off point determination. Loss of membranous CD44v6 was associated with pT stage ( P  = 0.016; sensitivity 85.8%, specificity 20.1%), lymph node metastasis ( P  = 0.015; sensitivity 52.8%, specificity 55%), an infiltrating tumour margin ( P  < 0.001; sensitivity 71.4%, specificity 40%) and adverse prognosis ( P  = 0.011; hazard ratio 0.79, 95% confidence interval 0.7, 0.9), but was not an independent prognostic factor on multivariable analysis. Loss of expression occurred at the invasive front in both primary and metastatic lesions ( P  < 0.001).
Conclusions:  This study outlines an approach to help standardize the immunohistochemical evaluation of CD44v6 and similar markers in colorectal cancer and highlights a significant role for loss of membranous CD44v6 expression in colorectal cancer progression and prognosis.     

E-cadherin在结直肠癌中的表达及其与侵袭转移的关系

目的：探讨E-cadherin在结直肠癌（colorectal carcinoma,CRC）中的表达及其与侵袭转移的关系。方法：采用免疫组织化学SABC法及原位杂交技术检测E-cadherin mRNA和蛋白在大肠正常黏膜、大肠腺瘤和CRC组织中的表达。结果： E-cadherin的mRNA和蛋白在CRC中的阳性率显著低于正常黏膜组织和腺瘤（P＜0.01）;随着CRC分化的降低和Dukes分期的增加,E-cadherin表达阳性率降低;E-cadherin的阳性率在有淋巴结和远处器官转移的CRC中均显著低于未转移组（P＜0.01,P＜0.05）。结论：E-cadherin表达减少或缺失在CRC的侵袭转移过程中发挥重要的作用。     

Epithelial hyaluronic acid and CD44v6 are mutually involved in invasion of colorectal adenocarcinomas and linked to patient prognosis

Desmoplastic stroma of colorectal adenocarcinomas contains a variety of extracellular matrix molecules, including hyaluronic acid (HA). Overexpression of the HA receptor CD44 and, in particular, its splicing variant CD44v6 has been described as a prognostic factor for patients with colorectal adenocarcinomas in some studies, but converse reports also exist. Our hypothesis is that these divergent results may be related to the fact that the function of CD44v6 depends on the HA content of cell-surrounding matrix. Therefore, we studied the expression of HA and CD44v6 in tissue samples of 145 patients suffering from colorectal adenocarcinomas using immunohistochemistry. Expression of HA was separately evaluated in tumor epithelium and stroma. We additionally examined the influence of HA on invasion and adhesion of colorectal adenocarcinoma cells in vitro. The results show that epithelial HA expression was not correlated with tumor stage but with lymph-node or distant metastasis. Patients with tumors expressing epithelial HA had a decreased overall survival (P=0.017) as well as tumors with coexpression of epithelial HA and CD44v6 (P=0.011). The latter issue remained an independent prognostic factor in multivariate analysis (relative risk 5.06; 95% confidence interval, 1.18–21.57; P=0.028). HA exclusively stimulated in vitro invasion of CD44v6-expressing cells. This stimulation was partly reversed by an anti-CD44v6 antibody. Our findings suggest that the adverse prognostic effect of CD44v6 in colorectal adenocarcinoma might be restricted to those tumors that have pericellular HA.