Prediction of treatment outcome by CD44v6 after total mesorectal excision in locally advanced rectal cancer

BACKGROUND: The purpose of this study was to investigate the significance of CD44 variant 6 (CD44v6) in predicting the treatment outcome of locally advanced adenocarcinoma of the rectum after total mesorectal excision (TME). METHODS: Expression of CD44v6 protein was detected using immunohistochemistry in 179 patients with pathologically confirmed stage II or III rectal adenocarcinoma. All patients were treated with TME, and neither neoadjuvant nor adjuvant radiotherapy were used. The correlation between the expression of CD44v6 and other disease-related characteristics with treatment outcome was investigated. RESULTS: The 5-year overall survival and disease-free survival rates were 66.75% and 65.77%, respectively, and the overall locoregional recurrence rate was 8.13% for the entire group of patients. CD44v6 was present in 41.9% of all patients. Multivariate analysis revealed that CD44v6 status and pelvic nodal metastasis were independent risk factors for the rate of distant metastases (P = 0.036 and 0.035, respectively), disease-free survival (P = 0.009 and 0.016, respectively), and overall survival (P = 0.048 and 0.034, respectively). Lymph node metastasis was the only independent risk factor for locoregional recurrence (P = 0.048), and a trend was found for CD44v6 on predicting the locoregional recurrence (P = 0.06) with both stage II and III diseases. CD44v6 is significantly associated with locoregional recurrence in stage III rectal cancer (hazard ratio 6.02, 95% confidence interval 1.25-29.0; P = 0.018), and the overall locoregional recurrence was significantly higher for patients with positive expression of CD44v6 than for those with negative expression (17.63% vs 6.62%; P = 0.026). CONCLUSION: CD44v6 expression in cancer cells is a sensitive marker for predicting the treatment outcome in patients with stage II and III adenocarcinoma of the rectum after TME and may be used to determine the necessity of adjuvant treatment. However, further investigations are needed to determine the clinical application of CD44v6 and its reliability.     

CD44v6在预测直肠癌全系膜切除手术后局部复发的价值

背景与目的：直肠癌全系膜切除术（TME）的应用显著改善了中高位直肠癌患者的预后,但是对影响局部复发的危险因素仍然有待进一步研究。本研究对行根治性TME手术的进展期直肠癌患者的临床病理资料和免疫组化资料进行分析,进一步探索影响局部复发的高危因素。方法：分析179例行TME手术的Ⅱ、Ⅲ期直肠癌患者临床病理资料以及免疫组化检测CD44v6表达水平和预后之间的关系。结果：所有患者随访1-90个月,中位随访57个月。5年生存率和5年无病生存率分别为66.75%和65.77%。CD44v6和淋巴结转移状况是与总的生存时间和无病生存时间均相关的独立的预后危险因素。CD44v6表达水平是影响Ⅲ期直肠癌患者局部复发的独立危险因素。结论：CD44v6是预测Ⅲ期直肠癌TME术后局部复发的重要分子标记物。     

E-cadherin, CD44s and CD44v6 correlate with tumour differentiation in colorectal cancer

Cell adhesion molecules (CAMs) are cell surface glycoproteins that are important in cell-cell and cell-matrix interactions and play an important role in cell growth and differentiation. We examined immunohistochemically CD44s, CD44v6 and E-cadherin expression in 86 formalin-fixed, paraffin-embedded primary tumours and 5 metastases. Lower levels of CD44s, CD44v6 and membranous E-cadherin expression were significantly associated with higher tumour grade (p=0.022, p=0.016 and p= 0.041, respectively). Moreover, CD44v6 and membranous E-cadherin expression were correlated with the depth of primary tumour invasion (p=0.030 and p=0.020, respectively), and increased expression of CD44v6 and decreased membranous E-cadherin expression were associated with increased primary tumour invasion. The results suggest that these CAMs are associated with tumour differentiation and invasion in locally advanced and metastatic colorectal carcinoma.     

CD44V6在非小细胞肺癌组织中的表达及其意义

 目的　探讨CD44v6在非小细胞肺癌（NSCLC）组织中的表达及其对预后判定的意义。方法　应用免疫组织化学方法对1995年12月至2002年9月62例手术NSCLC组织标本进行CD44v6的检测。结果　62例NSCLC中CD44v6阳性表达38例，阳性率为61.3 ％，CD44v6阳性表达率与淋巴结转移及 3年生存率有密切关系，不同肿瘤分化程度、病理分型及TNM分期间差异无统计学意义。结论　NSCLC患者CD44v6阳性表达与肿瘤淋巴结转移及患者生存率关系密切，可以作为临床评估肿瘤转移及判断预后的指标。     

CD44 v6与非小细胞肺癌的研究进展

CD44是一种跨膜糖蛋白,是由单一基因所编码的具有高度特异性的单链膜表面糖蛋白家族。其主要参与细胞与细胞、细胞与基质之间的特异性黏附过程。 CD44v6是CD44家族的成员之一,其与非小细胞肺癌转移和预后的相关性成为近几年来研究的一大热点,本文就当前CD44 v6与非小细胞肺癌的研究进展做一综述。     

乳腺癌组织CD44v6蛋白的表达及其临床意义的研究

目的 研究肿瘤转移相关基因CD44v6在乳腺癌组织中的表达情况及其临床意义.方法 用免疫组化SP法对77例乳腺病变组织进行CD44v6蛋白检测,并结合临床、病理形态学资料分析其临床意义.结果 12例乳腺良性病变组织中CD44v6蛋白表达均为阴性;65例乳腺癌组织中CD44v6表达阳性率为64.6%(42/65);在腋淋巴结阳性、阴性组的阳性率分别为100%、25.8%(P<0.05);组织学分级中Ⅰ、Ⅱ、Ⅲ级表达率分别为9.1%、61.8%、100%(P<0.001).Logistic多因素回归分析显示,CD44v6蛋白表达与腋淋巴结转移、肿瘤大小和组织学分级有显著相关性.结论 CD44v6蛋白可作为乳腺肿瘤恶性转化、转移和预后评估的一个重要指标.     

CD44v6与可溶性CD44v6在胃癌中的表达及与预后的关系

目的 探讨CD44v6与可溶性CD44v6(sCD44v6)在胃癌中的表达及与胃癌生物学行为和预后的关系.方法 应用免疫组化S-P法检测103例胃癌组织和10例正常胃黏膜标本的CD44v6表达,并对患者进行术后随访,随访期为3～91个月;应用酶联免疫吸附(ELISA)法检测86例胃癌、30例胃溃疡患者和30例健康人外周血血清中sCD44v6的浓度,并对患者进行术后随访,随访期为1～91个月.结果 (1)CD44v6在正常胃黏膜中不表达,而在胃癌中的表达率为60.2%;CD44v6的表达与淋巴结转移、TNM分期、脉管是否存在癌栓以及Borrmann分型有关(P＜0.05),而与胃癌浸润深度、是否远处转移、分化程度以及患者的生存率无关(P＞0.05);9例伴有肝转移的胃癌患者中,有7例CD44v6为强阳性表达.(2)胃癌患者外周血血清中sCD44v6的浓度明显高于胃溃疡组和健康对照组(P＜0.01);胃癌根治术后患者血液中sCD44v6的浓度比术前明显下降(P＜0.01),而姑息术后患者的浓度变化却不明显(P＞0.05);sCD44v6的浓度与胃癌浸润深度、淋巴结转移、是否远处转移、脉管是否存在癌栓、Borrmann分型以及分化程度无关;sCD44v6浓度较高组的生存率较sCD44v6浓度较低组高,且差异有统计学意义(P=0.0281),但经Cox回归分析显示,sCD44v6的浓度与生存期有关(P=0.415),而手术方式却与生存期有关(P=0.000).(3)胃癌组织中CD44v6的表达与外周血血清中sCD44v6的表达无明显平行关系(P＞0.05).结论 CD44v6的表达对评估胃癌生物学行为有参考价值,但是否与预后有关仍需探讨;sCD44v6的表达对胃癌辅助诊断、手术彻底性判定及生物学行为评估有一定的意义;CD44v6与sCD44v6的表达无明显平行关系.     

CD44v6 is not a prognostic factor in primary breast cancer

Background: CD44 is an adhesion molecule and represents a highly variable family of isoforms. The isoform CD44v6 has been associated with metastasis formation and poor prognosis in animal models and human colon cancer. Results of studies in primary breast cancer are relatively small and contradictory.Patients and methods: The immunohistochemical expression of CD44v6 was studied in a series of 338 patients with primary breast tumours, uniformly staged and treated in a single center with a long median follow-up of 128 months. The prognostic significance of CD44v6 as well as the correlation with several clinicopathological features were analysed.Results: Two hundred nineteen of 338 (64.8%) of the breast cancers were CD44v6-positive (>5% of tumour cells with positive staining). CD44v6 expression had no value for prognosticating disease-free or overall survival at this or any other cut-off point.Conclusion: CD44v6 expression is not a prognostic factor in primary breast cancer.     

Prognostic value of CD44 and CD44v6 expression in patients with non-small cell lung cancer: meta-analysis

We sought to clarify the prognostic value of CD44 in survival of patients with non-small cell lung cancer (NSCLC). We performed a meta-analysis of relevant literature to aggregate the available survival results, using studies published in English until March 2014. Eligible studies dealt with CD44, CD44 standard form (CD44s) and CD44 variant 6 (CD44v6), assessment in NSCLC patients on primary lesions and reported survival data according to CD44 and CD44 isoforms expression. We aggregated 10 trials (5 trials for CD44v6, 3 trials for CD44, and 2 trials for CD44s) comprising 1,074 patients, in this meta-analysis. The combined hazard ratio (HR) with CD44v6 and CD44s was 2.39 (95 % confidence interval (CI) 1.69–3.37) and 1.64 (95 % CI 1.06–2.52), respectively. It associated high CD44v6 and CD44s expression with poor survival in NSCLC patients. However, CD44 overexpression did not significantly correlate with survival in patients with NSCLC (HR 1.44; 95 % CI 0.72–2.89). Our meta-analysis shows that CD44v6 and CD44s overexpression indicates poor prognosis for NSCLC patients. However, the high CD44 expression is not significantly correlated with survival for patients with NSCLC.     

骨桥蛋白OPN和黏附分子CD44v6在肺癌中的表达

背景与目的 近年来关于细胞表面黏附分子（CD44）与肺癌关系的相关研究较多，而对骨桥蛋白（OPN）的研究还不太多。本研究旨在探讨OPN和CD44v6在肺癌中的表达水平及其相互关系。方法 应用免疫组织化学方法对78例肺癌组织标本进行OPN和CD44v6检测。结果 65例非小细胞肺癌中OPN和CD44v6阳性表达率分别为58、46％、66．15％，13例小细胞肺癌中OPN和CD44v6表达均为阴性（P〈0.01）。OPN和CD44v6阳性表达率与患者TNM分期有密切关系（P〈0．01），而与细胞分化程度无明显关系（P〉0.05）。OPN和CD44v6在肺癌中的表达呈正相关（r=0．255，P〈0.05）。结论 OPN和CD44v6的表达同肺癌病理类型和分期有密切关系，二者在肺癌转移中可能起协同作用，有望作为临床评估非小细胞肺癌进展及预测肿瘤转移潜能的指标。     

CD44v6、PCNA在胃癌中的表达及其临床意义

目的　探讨CD4 4v6、PCNA在胃癌中的表达及其临床意义。方法　采用链霉菌抗生物素蛋白—过氧化物酶 (SP)对 81例胃癌组织进行CD4 4v6、PCNA检测。结果　CD4 4v6、PCNA在胃癌组织中的表达分别为5 1 9%、4 9 4 %。CD4 4v6、PCNA的表达与胃癌的病理类型无关 (P >0 0 5 ) ,但与胃癌的肿瘤浸润深度、病理分级、有无淋巴结转移、肝转移密切相关 (P <0 0 1)。结论　CD4 4v6、PCNA蛋白的表达水平不但能反映胃癌的增殖与分化程度 ,而且与其转移密切相关 ,可作为胃癌预后的重要指标。     

Soluble CD44 v5 and v6 in serum of patients with breast cancer. Correlation with expression of CD44 v5 and v6 variants in primary tumors and location of distant metastasis

Primary breast cancers were shown to overexpress CD44 v5 and v6 at the plasma membrane. However, the clinical significance of this overexpression remains unclear. Overexpression of CD44 v5 and v6 in primary breast cancers was found to correlate with metastasis and poor prognosis by some investigators, yet this correlation could not be confirmed by others using different antibodies. In this study the influence of metastatic disease, the site of metastasis, and the amount of CD44 v5 and v6 expression in the primary tumor on serum levels of the soluble forms of CD44 v5 and v6 (sCD44 v5 and v6) in breast cancer patients was investigated. Soluble CD44 v5 and v6 serum levels were measured by enzyme linked immuno sorbent assay in a group of breast cancer patients who developed metastases in various organs and in another group of patients with single organ metastasis. For control, sCD44 v5 and v6 levels were measured in breast cancer patients who remained free of metastasis and in healthy blood donors. Expression of plasma membrane bound CD44 v5 and v6 in the primary tumors of the patients with metastasis in various organs was correlated to sCD44 v5 and v6 levels in serum. Furthermore the size of sCD44 v6 was analyzed by immunoblot using a monoclonal antibody directed against CD44 v6. When metastases were detected, sCD44 v5 and v6 serum levels were increased as compared to levels measured one month after tumor surgery in patients free of metastases (p = 0.0025 and p = 0.0004). Six of 19 and 6 of 20 patients had sCD44 v5 and v6 serum levels above a cut-off level of 85 and 275 ng/mL, respectively. In these cases expression of CD44 v5 and v6 in the primary cancers was also elevated. Low sCD44 v5 and v6 serum levels were associated with weak expression of CD44 v5 and v6 in the respective primary cancers. As shown by statistical analysis of sCD44 v5 and v6 levels in 57 patients with single organ metastases, elevated sCD44 v6 levels but not sCD44 v5 levels were associated with metastases in liver or bone (p = 0.0025). Immunoblot analysis of soluble CD44 proteins in serum revealed two CD44 v6 specific signals of approximately 120 and 170 kDa. Increased sCD44 v5 and v6 serum levels in patients with breast cancer were influenced by the amount of CD44 v5 and v6 expression in the primary tumor by the site of metastasis. Elevated sCD44 v6 serum levels were preferentially found in patients with metastases in liver or bone.     

CD44V6表达与胰腺癌增殖,转移及预后关系的研究

目的：探讨ＣＤ４４Ｖ６表达与胰腺癌增殖活性、淋巴结转移以及预后的关系。方法：应用免疫组ＬＳＡＢ法检测４７例胰腺癌组织中ＣＤ４４Ｖ６和ＰＣＮＡ的表达。结果：予性率为５７．４％（２７／４７）,与胰吕组织学类型及分级无关,伴淋巴结转移者ＣＤ４４Ｖ６阳性率（８１．０％,１７／２１）,明显高于无淋巴结转移者（３８．５％,１０／２６）,两者间有极显著性差性差异（Ｘ＾２＝８．５８,Ｐ〈０．０１）,ＣＤ４４Ｖ６阴     

CD44v6在胃癌中的表达

[目的]研究胃癌CD44v6的表达及意义。[方法]应用免疫组织化学ABC法 ,研究85例胃癌手术标本中CD44v6的表达。[结果]胃癌原发灶中CD44v6表达阳性率为61 2%(52/85)。CD44v6表达阳性率在进展期胃癌(66 7%)、累及浆膜层胃癌(72 2%)、淋巴结阳性胃癌(73 2%)均高于早期胃癌(30 8%)、未累及浆膜层胃癌(41 9%)、淋巴结阴性胃癌(37 9%)(P<0 05或P<0 01)。[结论]CD44v6可能参与胃癌的浸润和淋巴结转移过程。检测胃癌CD44v6的表达 ,有助于对胃癌生物学行为的了解及对患者预后的判断     

肺癌骨桥蛋白和CD44v6的表达与转移关系的研究

目的：探讨骨桥蛋白（osteopontin，OPN）和粘附分子CD44v6在肺癌组织中的表达及其与肺癌转移的关系。方法：应用免疫组织化学技术（SP）检测57倒肺癌组织中OPN与CD44v6的表达水平，并将结果与30例良性肺部疾病组织中OPN及CD44v6水平相比较。结果：肺癌组织中OPN和CD44v6阳性表达率分别为57．9％（33／57）和54．4％（31／57），显著高于良性肺部疾病（肺部炎性假瘤）组织（P〈0．05），阳性表达率分别为16．7％和10．0％，肺癌组织中OPN与CD44v6的表斌足正相关.Kendall’s tau—b-0.503，P〈0．05；OPN与CD44v6在发生淋巴结转移的肺癌组织中阳性表达率分别达71．1％（27／38）和65．8％（25／38），显著高于无淋巴结转移的肺癌组织中阳性表达率（P〈0．05）。结论：OPN、CD44v6可能参与了肺痛的发生、发展和转移，联合检测它们的表达可作为肺癌生物学行为的一项评估指标。     

CD44v6基因在宫颈癌组织中的表达及其临床意义

目的:探讨CD44v6基因在宫颈癌组织中的表达情况及其临床意义。方法:用免疫组织化学S-P法,检测56例宫鳞癌,32例宫颈腺癌中CD44v6蛋白的表达情况并分析相关的临床病理因素。结果:CD44v6表达与宫颈癌组织学类型无关;无论宫颈腺癌或鳞癌,淋巴结转移组中CD44v6阳性表达明显高于无淋巴结转移组（P<0.05）;CD44v6表达与宫颈癌临床分期、病理分级、病灶大小无关（P>0.05）。结论:CD44v6在宫颈癌淋巴结转移及癌细胞分化过程中可能起着重要作用,对早期预测癌细胞的转移潜能、判断宫颈癌预后具有一定的临床意义。     

非小细胞肺癌CD44v6的表达及其在患者预后判定中的作用

背景与目的CD44v6的过度表达与人类多种恶性肿瘤的发生、发展和转移密切相关。本研究旨在观察CD44v6在非小细胞肺癌中的表达及其在患者预后判定中的作用。方法采用RTPCR和免疫组化法,对52例非小细胞肺癌患者手术标本进行CD44v6检测,并随访。结果免疫组化法和RTPCR法测得52例肺癌组织中CD44v6阳性表达率分别为69.2%和75.0%。低分化肺癌组织中CD44v6阳性表达率显著高于高分化和中分化肺癌(P<0.05),有淋巴结转移者显著高于无淋巴结转移者(P<0.01),Ⅲ期显著高于Ⅰ期和Ⅱ期(P<0.05)。CD44v6阴性表达者生存率显著高于CD44v6阳性表达者(P=0.0115)。多元logistic回归分析显示,CD44v6阳性表达(P=0.048)和pTNM分期(P=0.035)对生存率有显著影响。结论肺癌中存在CD44v6过度表达,检测CD44v6的表达有助于预测肺癌患者的预后。     

31例乳腺癌CD44v6和CD44intron 9检测

［目的］探讨 ＣＤ ４４ ｍＲＮＡ异常表达和拼接与乳腺癌的相关意义。［方法］采用 ｒｅｖｅｒｓｅ ｔｒａｎｓｃｒｉｐｔｉｏｎ－ ｐｏｌｙｍｅｒａｓｅ ｃｈａｉｎｒｅａｃｔｉｏｎ（ＲＴ－ＰＣＲ）方法检测了３１例乳腺癌组织、１７例乳腺癌周组织中ＣＤ ４４ｖ６和ＣＤ ４４ ｉｎｔｒｏｎ ９的表达。［结果］乳腺癌患者癌组织、癌周组织中ＣＤ４４ｖ６的表达率均为１００％（３１／３１,１７／１７）,ＣＤ４４ ｉｎｔｒｏｎ９的表达率分别为８３．８７％（２６／３１）,９４．１２％（１６／１７）,经ｘ２检验,ＣＤ ４４ｖ６、 ＣＤ ４４ ｉｎｔｒｏｎ ９在乳腺癌及癌周组织中的表达差异无显著性。［结论］ ＣＤ ４４ｖ６、 ＣＤ ４４ ｉｎｔｒｏｎ ９在乳腺癌患者中的表达具有普遍性,其表达与乳腺癌的转移无显著相关性。     

胃肠道间质肿瘤CD44s和CD44v6的表达及其意义

目的:探讨CD44s和CD44v6在胃肠道间质肿瘤(GISTs)中的表达及其意义。方法:应用免疫组织化学方法检测65例胃肠道间质肿瘤中CD44s和CD44v6的表达。结果:65例GISTs中,CD44s63例阳性,阳性率达96.9%,其中阳性强度>4分者57例(87.7%),>6分者43例(66.2%)。低度、中度、高度恶性潜能组阳性强度>4分者分别为93.8%,100%,81.1%,3组之间表达水平无显著差异(P>0.05);>6分者分别为87.5%,75.0%,54.1%,3组之间表达水平有显著差异(P<0.05)。CD44v640例阳性,阳性率为61.5%,其中阳性强度>4分者19例(29.2%),阳性强度>6分者6例(9.2%)。低度、中度、高度恶性潜能组阳性强度>4分者分别为18.8%,33.3%,32.4%,3组之间表达水平无显著差异(P>0.05);>6分者分别为0%,8.3%,13.5%,3组之间表达水平无显著差异(P>0.05)。结论:CD44s表达与GISTs的恶性潜能呈负相关。CD44v6在GISTs中很少有表达,与GISTs的恶性潜能无明显相关性。免疫组化法检测CD44s可以作为预测GISTs恶性潜能的相关指标之一。