ICAM-1和CD44v6在结、直肠癌中的表达及临床意义

目的:了解ICAM-1和CD44v6在结、直肠癌中的表达,探讨它们与结直肠癌侵袭与转移的关系.方法:应用免疫组织化学pv-9000二步法检测ICAM-1和CD44v6在40例结直肠癌和30例大肠良性腺瘤组织中的表达情况,并分析其与结直肠癌临床病理特征的关系.结果:40例结、直肠癌和30例大肠良性腺瘤中,ICAM-1的表达阳性率分别是72.5%(29/40)、33.3%(10/30),CD44v6的表达阳性率分别是88.9%(27/40)、26.7%(8/30). ICAM-1和CD44v6的表达与年龄、性别、肿瘤细胞分化程度无关,但与淋巴结转移、Dukes分期具有相关性(p<0.05).有淋巴结转移、Dukes分期在C+D期者,ICAM-1和CD44v6的表达阳性率均明显升高.ICAM-1和CD44v6在大肠良性腺瘤中呈低表达或不表达.ICAM-1和CD44v6两者均阳性表达时,其预测结、直肠癌淋巴结转移的特异性升高,有一定的临床意义.结论:CD44v6和ICAM-1的阳性表达预示结直肠癌具有较强的侵袭转移能力,可作为预测结直肠癌转移潜能的生物学指标.     

CD44V6和MMP-2在甲状腺肿瘤中的表达及其临床意义

目的:研究黏附分子CD44V6和基质金属蛋白酶-2(MMP-2)在甲状腺癌中的表达、相互关系及其与甲状腺癌侵袭转移的相关性.方法:采用SP免疫组化法检测114例甲状腺肿瘤组织中CD44V6和MMP-2的表达.结果:CD44V6和MMP-2在35例甲状腺乳头状癌(Papillary Thyroid Carcinoma,PTC)中阳性表达率分别为70.6%和73.5%,在41例甲状腺滤泡癌(Follicular Thyroid Carcinomas,FTC)中阳性表达率分别为70.7%和75.6%,均高于甲状腺腺瘤和结节性甲状腺肿组织中的表达,差异具有统计学意义(P＜0.05).在甲状腺癌组织中MMP-2和CD44V6的表达具有显著相关性(r=0.4828,P＜0.001).且两者表达与甲状腺癌的临床分期及有、无淋巴结转移显著相关.结论:CD44V6和MMP-2的表达与甲状腺癌分化程度、浸润和转移关系密切.CD44V6和MMP-2检测对甲状腺癌的诊断、分化程度、转移趋势和预后评估具有重要参考价值,是甲状腺癌侵袭、转移和预后判断的分子标志物.     

胃癌CD44v6 mRNA及其蛋白表达与临床病理特征的关系

目的探讨细胞粘附分子CD44v6 mRNA及其蛋白表达与胃癌临床病理学行为和患者预后的关系. 方法应用高敏感性催化信号放大系统(catalyzed signal amplification,CSA)原位杂交和免疫组化技术,对17例早期胃癌、21例中期胃癌和57例晚期胃癌组织进行CD44v6 mRNA及其蛋白检测,并结合肿瘤的病理学行为和临床随访资料进行分析.结果在胃癌中,CD44v6 mRNA及其蛋白的表达阳性率分别为85.3%和82.1%.CD44v6 mRNA及其蛋白表达阳性率在晚期胃癌明显高于早、中期胃癌(P<0.05).CD44v6 mRNA表达与蛋白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<0.05).结论 CD44v6 mRNA及其蛋白异常表达与胃癌的临床病理生物学行为密切相关,特别是与胃癌细胞的转移潜能和胃癌患者的不良预后密切相关.CD44v6蛋白水平的表达可以间接反映其mRNA转录水平,并可作为预测胃癌转移潜能和患者预后的一个新的生物学指标.     

胃癌中CD44v6 表达及与微血管密度和生物学行为的关系

目的:探讨CD44v6在胃癌中的表达及其与微血管密度(microvessel density,MVD)和生物学行为的关系。方法:采用免疫组化法检测80例胃癌组织CD44v6、CD34的表达,以CD34标记肿瘤微血管,并在显微镜下计数微血管密度(MVD)。结果:CD44v6在胃癌组织中的表达与肿瘤浸润深度、临床分期、淋巴结转移相关(P<0.05),CD44v6强阳性表达组中MVD明显高于CD44v6阴性表达组(P<0.05)。结论:CD44v6的表达和MVD计数是反映胃癌生物学特性的良好的指标,对判断胃癌的浸润转移具有一定的临床意义。     

非小细胞肺癌中E-钙粘素和CD44v6的表达及其意义

为了探讨E-钙粘素(E-cadherin,E-cad)和白细胞分化抗原变异型6(CD44v6)在非小细胞肺癌(NSCLC)中的表达及临床意义,采用免疫组织化学(SP法)对65例NSCLC和20例癌旁组织中E-cad和CD44v6的表达进行研究。结果显示E-cad在肺癌组织中的阳性表达率(32.31%)显著低于癌旁组织(75.00%)(P<0.01),且与NSCLC的TNM分期、淋巴结转移呈负相关(P<0.05),与分化程度呈正相关(P<0.01),而与组织分型无关(P>0.05);CD44v6的阳性表达率与组织分型和分化程度无关(P>0.05),而与TNM分期和淋巴结转移呈正相关(P<0.05,<0.01)。两者在NSCLC中的表达显著相关(P<0.05)。因此检测E-cad和CD44v6的共同表达将是指导临床治疗及估计预后的有意义指标,可应用于临床预后的综合评价。     

环氧化酶-2和CD44v6蛋白在宫颈鳞癌中表达及临床意义

探讨环氧化酶-2(cyclooxy-genase-2,COX-2)和CD44v6蛋白在官颈上皮内瘤样病变(CIN)和浸润宫颈鳞癌(ICC)中的表达及其意义.应用免疫组织化学方法,检测45例ICC、25例CIN和10例正常宫颈组织(NCE)中COX-2和CD44v6蛋白的表达水平,并结合临床病理特征进行分析.结果表明,在ICC、CIN和NCE中,COX-2蛋白表达阳性率分别为82.2%(37/45)、40%(10/25)和0%(0/10),差异有显著性(P＜0.05);CD44v6蛋白表达阳性率分别为88.9%(40/45)、44%(11/25)和20%(2/10),差异有显著性(P＜0.05).COX-2和CD44v6蛋白表达与ICC的分化程度和淋巴结转移相关(P＜0.05),但与临床分期无关(P＞0.05).COX-2和CD44v6可能参与了调控ICC的发生、发展过程,其高表达预示ICC预后不良.     

CD44v6和PTEN在胃印戒细胞癌中的表达意义

目的:探讨CD44v6和PTEN在胃印戒细胞癌组织中的表达与临床病理特征及预后之间的关系.方法:应用免疫组织化学SP二步法,检测73例胃印戒细胞癌组织中CD44v6及PTEN的表达,分析CD44v6、PTEN与胃印戒细胞癌浸润深度、淋巴结转移、器官转移、临床分期和三年生存率的关系.结果:73例胃印戒细胞癌组织中CD44v6阳性率为78.1%(57/73),PTEN阳性表达率为34.2%(25/73),PTEN表达与器官转移、临床分期有差异(P＜0.05),CD44v6、PTEN表达均与胃印戒细胞癌浸润深度、淋巴结转移有差异(P＜0.05).两者之间Spearman等级表达呈负相关(r=-0.214,P＜0.05);Kaplan-Meier生存分析显示PTEN阴性组三年生存率16.1%显著低于PTEN阳性组66.9%(P＜0.01).结论:进行CD44v6和PTEN免疫组织化学检测对评估胃印戒细胞癌的预后具有一定意义.     

大肠癌及癌旁粘膜中CD_(44)、nm23-H_1的表达及其临床病理意义

探讨 CD44 、nm2 3- H1 的表达与大肠癌侵袭及转移的关系。应用免疫组化 SABC法检测 5 7例大肠癌组织及相应的癌旁粘膜、正常粘膜组织中 CD44 v6 、 CD44 S、 nm 2 3- H1 的表达 ,并分别比较其与大肠癌侵袭及淋巴结转移的关系。结果显示大肠癌组织 CD44 v6 的阳性率 (70 .18% )显著高于癌旁粘膜 (阳性率为 12 .0 2 % )及正常粘膜 (阳性率为 0 ) (P<0 .0 5 ) ;大肠癌组织 CD44 S和 nm2 3- H1 的阳性率 (分别为 42 .11%和 5 4.39% )显著低于癌旁粘膜 (分别为 89.47%和 91.2 3% )及正常粘膜(分别为 10 0 %和 94.74% ) (P<0 .0 5 )。CD44 v6 、nm2 3- H1 的表达与大肠癌浸润深度及淋巴结转移有相关性 (P<0 .0 5 ) ,与大肠癌分化程度无关 (P>0 .0 5 )。CD44 v6 与 nm2 3- H1 蛋白表达无明显相关性 (rs=- 0 .117,P>0 .0 5 )。结果表明 CD44 、nm2 3-H1 可作为大肠癌侵袭与淋巴结转移的重要标志     

胃癌及相应癌旁组织中VEGF、CD34、CD44v6的检测及临床意义

目的:探讨血管内皮生长因子(Vascular endothelial growth factor,VEGF)、CD34和CD44v6在胃癌及相应癌旁组织中的表达及其与临床病理意义.方法:应用免疫组化技术检测60例胃癌以及相应癌旁组织中VEGF、CD34和CD44v6的表达.结果:胃癌组织VEGF阳性率为71.67%(43/60)明显低于癌旁组织88.34%(53/60),两组间有显著性差异(P=0.022);VEGF阳性表达与胃癌病理分级、浸润深度、淋巴结转移和临床分期密切相关(P＜0.05).癌旁组织中微血管密度(MVD)明显高于癌组织MVD(P=0.000),有淋巴结转移癌组织中MVD高于无淋巴结转移者(P=0.043),并随浸润深度、临床分期MVD升高(P=0.046,P=0.000).癌旁组织中CD44v6阳性率为48.34%(29/60)低于癌组织的61.67%(37/60),两者无明显差别.CD44v6的阳性率随胃癌浸润的加深而升高,与淋巴结转移和TNM分期呈正相关.VEGF、CD34及CD44v6三指标间两两相关(P＜0.05).结论:VEGF、CD34和CD44v6三者联合检测有助于判断胃癌的浸润、转移及预后情况.     

凋亡抑制基因livin与survivin在乳腺癌中的表达差异

目的探讨凋亡抑制基因livin在乳腺癌发生、发展中的作用及其与survivin基因的表达和乳腺癌生物学行为之间的关系。方法采用逆转录聚合酶链反应(RT-PCR)检测44例乳腺癌组织、40例癌旁正常组织及4个乳腺癌细胞系中livinmRNA和survivin mRNA的表达,并用免疫组化(IHC)EnVision法检测上述组织和细胞中livin和survivin蛋白的表达。结果livin mRNA和survivin mRNA在乳腺癌组织中的阳性表达率分别为72.7%(32/44)和61.4%(27/44),在癌旁正常组织中的阳性率分别为7.50%(3/40)和5.00%(2/40),二者在癌组织中的表达均显著高于在正常组织中的表达(P<0.01)。livin和survivin蛋白表达情况与mRNA结果相似(P<0.01)。livin和survivin在乳腺癌组织中的表达无显著相关性(P>0.05)。4个乳腺癌细胞系中均有survivin mRNA和蛋白的表达,而MCF-7及MDA-MB-435细胞系中呈阴性表达。survivin基因在伴有淋巴结转移的乳腺癌组织中的表达明显高于无淋巴结转移的乳腺癌组织(P=0.0047),livin在雌激素受体(ER)阴性或者Her2/neu阳性表达的乳腺癌中的阳性率有升高的趋势,但并无显著性差异(P>0.05)。结论livin和survivin基因在人乳腺癌组织中表达上调,提示其可能在乳腺癌发生、发展中起重要促进作用,sur-vivin和淋巴结转移的密切关系表明它的高表达可能反映患者较差的预后。livin和survivin基因一样可能成为乳腺癌治疗中的一个靶基因。     

真核细胞起始因子4E与C-myc在甲状腺乳头状癌中的表达

目的观察真核细胞起始因子4E(eukaryotic initiation factor4E,eIF4E)及C-myc在甲状腺乳头状癌中的表达,并探讨两者间的相关性及它们与甲状腺乳头状癌的侵袭、转移等临床病理特征间的关系。方法采用免疫组化EnVin-sion法检测66例甲状腺乳头状癌、20例结节性甲状腺肿伴乳头状增生及上述病例的病变周围正常甲状腺组织中eIF4E和C-myc的表达情况。结果在正常甲状腺、结节性甲状腺肿伴乳头状增生及甲状腺乳头状癌中,eIF4E的阳性率分别为11.6%(10/86)、50.0%(10/20)和84.8%(56/66)(P<0.01),C-myc的阳性率分别为21.0%(18/86)、50%(10/20)和78.8%(52/66)(P<0.01)。eIF4E仅与乳头状癌的腺外侵袭和淋巴结转移有关(均P<0.05),C-myc仅与乳头状癌的淋巴结转移有关(P<0.01)。eIF4E及C-myc在乳头状癌中的表达呈正相关(rs=0.327,P<0.05)。结论与癌旁正常组织和良性病变相比,eIF4E和C-myc在甲状腺乳头状癌中存在过表达。eIF4E的过表达与甲状腺乳头状癌的腺外侵袭和淋巴结转移有关,C-myc的过表达与甲状腺乳头状癌的淋巴结转移有关,提示二者在甲状腺乳头状癌的进展中可能发挥重要的作用。     

宫颈癌中骨桥蛋白和CD44v6的表达及临床意义

目的探讨骨桥蛋白(OPN)和CD44v6在宫颈浸润癌中的表达及其意义。方法应用免疫组化SP法检测OPN和CD44v6在10例慢性宫颈炎、30例宫颈上皮内瘤样变及50例宫颈浸润癌组织中的表达。结果OPN在以上组织中的阳性表达率分别为10.00%(1/10)、36.67%和60.00%,慢性宫颈炎与宫颈浸润癌之间的表达差异有显著性(P<0.01);CD44v6阳性表达率分别为10.00%(1/10)、43.33%和68.00%,慢性宫颈炎与宫颈浸润癌之间的表达差异有显著性(P<0.01)。宫颈浸润癌组织中OPN和CD44v6表达均与患者年龄、肿瘤病理分级、组织学类型无关(P>0.05),而与淋巴结转移有关(P<0.05)。OPN与CD44v6的表达之间有显著正相关性(r=0.829,P<0.01)。结论OPN、CD44v6可能参与了宫颈癌的发生、发展和转移过程,联合检测它们的表达可作为判断宫颈癌的预后和术后复发的评估指标。     

Expression of metastasis associated proteins,CD44v6 and NM23-H1, in pediatric acute lymphoblastic leukemia

Two metastasis associated proteins, CD44v6 and NM23-H1, are expressed by normal lymphoid cells, the former serving as activation marker and the later as a constitutive protein. CD44v6 is considered as a marker of poor prognosis of various hematological cancers but its expression was not demonstrated in childhood acute lymphoblastic leukemia (ALL). On the other hand, NM23-H1 is considered as a differentiation inhibitory factor in various hematological cancers and as a marker of poor prognosis. Therefore we have analyzed the expression of CD44v6 and NM23-H1 in bone marrow of sixteen pediatric ALL patients using immunocytochemistry. For the first time, we have demonstrated the expression of CD44v6 protein epitopes on leukemic cells in a proportion of ALL cases (6/16), primarily in the medium/high risk group (except one case), suggesting a possible association to an unfavorable outcome. On the other hand, NM23-H1 protein expression was maintained in leukemic cells in 50% of both low and medium/high risk ALL cases. The majority of the pediatric ALL cases expressed only one of the metastasis associated proteins (10/16). This feature is highly similar to the observations made in several adult solid cancers. The potential of CD44v6 expression in leukemic cells as prognosticator in pediatric ALL has to be evaluated in a larger clinical trial.     

Expression of cytokeratin 20 and CD44 protein in upper urinary tract transitional cell carcinoma: cytologic-histologic correlation.

OBJECTIVE: To explore the potential utility of immunostaining for CK20 and CD44 protein isoforms in evaluating cases of upper urinary tract transitional cell carcinoma (UTTCC). STUDY DESIGN: Of 105 consecutive patients diagnosed cytologically with UTTCC, 33 subsequently underwent open surgical procedures. Cytologic samples from these patients retrieved by aspiration and biopsy, and corresponding surgical specimens were graded and staged using World Health Organization/International Society of Urologic Pathologists criteria. Immunostaining for CK20, CD44 standard (CD44s) and CD44v6 isoform (CD44-v6) was performed on all available cytologic and surgical materials. Expression levels and distributions of these markers were correlated semiquantitatively with grade and stage. RESULTS: Cytologically assigned grade correlated with final histologic grade in 19 of 31 cases examined (61%). However, tumor invasion was not accurately assessable in cytologic samples from the majority of these cases. Statistically significant correlations of both increasing tumor grade and stage with abnormal CK20 expression were found. In addition, a significant relationship between focal CD44 isoform expression loss and tumor grade was identified. However, CD44 isoform expression loss did not significantly correlate with increasing tumor stage. CONCLUSION: Although cytologic tumor grading of UTTCC was accurate, invasion could not be adequately assessed. As an adjunct to morphologic analysis, immunostaining for CK20 and CD44 may aid in the clinical evaluation of UTTCC tumor stage and biologic behavior prior to definitive therapy.     

BRAF mutation and RASSF1A expression in thyroid carcinoma of southern Italy

Aim of this work is to provide a detailed comparison of clinical‐pathologic features between well‐differentiated and poorly differentiated tumors according to their BRAF and RASSF1A status. We analyzed RASSF1A methylation by MSP and BRAF mutation by LCRT‐PCR with LightMix® kit BRAF V600E in neoplastic thyroid tissues. Immunohistochemical evaluation of RASSF1A expression was also performed by standard automated LSAB‐HRP technique. An overall higher degree of RASSF1A over‐expression than normal thyroid parenchyma surrounding tumors (P < 0.05) has been found in all malignant well‐differentiated lesions. Moreover, statistically significant higher levels of RASSF1A expression were observed in differentiated cancers associated to an inflammatory autoimmune background (P = 0.01). Amplifiable DNA for LC PCR with LightMix® kit BRAF V600E was obtained in nine PTCs, four FVPTCs, five ATCs, and one control. The V600E mutation was found in 13 of 18 (72%) tumors. BRAF was mutated in 6 of 9 (66%) classical PTC, in 2 of 4 (50%) follicular variant PTC and in all ACs (100%). The overall frequency of RASSF1A promoter methylation observed was 20.5% (9 cases out 44). Hypermethylation of RASSF1A in primary tumors was variable according to histotypes ranging from100% (5/5) in ACs to only 12.5% (4/32) in PTCs. We show a correlation between RASSF1A methylation status and RASSF1A protein expression. Finally, we conclude that BRAF V600E mutation and RASSF1A methylation were pathogenetic event restricted to a subgroup of PTC/FVPTCs in early stage and to clinically aggressive ATCs. J. Cell. Biochem. 114: 1174–1182, 2013. © 2012 Wiley Periodicals, Inc.     

Coexpression of EpCAM,CD44 Variant Isoforms and Claudin-7 in Anaplastic Thyroid Carcinoma

Background

Anaplastic thyroid cancer is considered to be one of the most aggressive human malignancies, and the mean survival time after diagnosis is approximately six months, regardless of treatments. This study aimed to examine how EpCAM and its related molecules are involved in the characteristics of anaplastic thyroid carcinoma.

Methodology/Principal Findings

Two differentiated thyroid cancer cell lines (TPC-1 and FTC-133), and two anaplastic thyroid cancer cell lines (FRO, ACT-1) were analyzed for expression of CD44 standard isoform (CD44s), CD44 variant isoforms, and EpCAM, and human aldehyde dehydrogenase-1 (ALDH1) enzymatic activity using flow cytometry. CD44s expression was higher in TPC-1 and FTC-133 than in the FRO and ACT-1, whereas ALDH1 activities were higher in FRO and ACT-1 than in TPC-1 and FTC-133. An inverse correlation between CD44s expression and ALDH1 activity was observed in all thyroid cancer cell lines. As for the expressions of CD44 variant isoforms, ACT-1 showed higher and FRO showed moderate CD44v6 expressions, whereas either TPC-1 or FTC-133 showed negative CD44v6 expression. EpCAM expressions in FRO and ACT-1 were higher than those in TPC-1 and FTC-133, and EpCAM expressions inversely correlated with those of CD44s. A positive correlation was observed between EpCAM expression and ALDH1 activity in thyroid cancer cell lines. In the RT-PCR analysis, the expression levels of EpCAM, caludin-7 and ALDH1 in FRO and ATC-1 cells were significantly higher than those in TPC-1 and FTC-133 cells. In clinical specimens of thyroid cancers, nuclear expression of EpCAM and high expression of CD44v6 were detected significantly more frequently in anaplastic carcinomas.

Conclusions/Significance

Our study suggests the possibility that EpCAM, together with CD44v6 and claudin-7 as well as ALDH1, may be involved in the development of the aggressive phenotype of anaplastic thyroid carcinoma. Our findings may suggest a novel therapeutic strategy for treatment of anaplastic thyroid carcinoma.     

微小RNA-205 在甲状腺乳头状癌中的表达及临床意义

目的:观察微小RNA(microRNA,miRNA,miR)-205在甲状腺乳头状癌(PTC)中的表达并探讨其临床意义。方法:收集自2014年1月至2014年12月在我院甲状腺外科住院治疗的甲状腺乳头状癌患者的术后新鲜病理组织45例,其中男14例,女31例,年龄24-69岁,平均45.5岁。结节性甲状腺肿28例,癌旁正常甲状腺组织5例。提取各组织中的miRNA,应用实时荧光定量聚合酶链反应(RT-q PCR)方法检测miR-205的表达情况。结果:甲状腺乳头状癌miR-205的表达量较非肿瘤组织(结节性甲状腺肿、癌旁组织)明显下调[(1.06±1.76)vs(3.19±4.88),P=0.038]。伴淋巴结转移的PTC组织中miR-205表达量明显低于无淋巴结转移的PTC组织[(1.21±1.80)vs(9.59±1.60),P=0.003]。miR-205的相对表达与PTC患者性别、年龄及浸润与否均无显著相关性,而肿瘤直径呈显著相关性。结论:miR-205在PTC中的表达异常下调,可能与PTC的发生、侵袭和转移有关。