Le^y抗原在卵巢上皮性肿瘤中的表达及意义

目的：探讨卵巢癌组织Le^y抗原的表达及其临床意义。方法：采用免疫组织化学SP法检测恶性、交界性、良性卵巢上皮肿瘤及正常卵巢组织中Le^y抗原的表达，并分析其与卵巢癌生物学特性之间的关系。结果：Le^y抗原在恶性卵巢上皮性癌中的阳性表达率为75．47％（40／53），明显高于交界性卵巢上皮性肿瘤（47．06％）及良性卵巢上皮性肿瘤（42．86％）（P均〈0．05）。正常卵巢组织中未检出Le^y抗原的表达。晚期卵巢上皮性癌的Le^y抗原的阳性表达率为84．21％，明显高于早期卵巢上皮性癌（53．33％），（P〈0.05）。结论：Le^y抗原与卵巢上皮性癌的发生、发展相关。Le^y抗原的表达可作为反映卵巢癌恶性潜能的一项新的指标。     

转录因子NR4A2在卵巢上皮性肿瘤组织中的表达及其临床意义

目的:探讨转录因子NR4A2在卵巢上皮性肿瘤组织中的表达及其临床意义。方法:采用免疫组化SP法检测39例卵巢上皮性癌、28例交界性卵巢上皮性肿瘤、27例良性卵巢上皮性肿瘤及17例正常卵巢组织中NR4A2蛋白的表达,分析其与临床病例参数的关系。结果:NR4A2蛋白在卵巢上皮性癌、交界性卵巢上皮性肿瘤、良性卵巢上皮性肿瘤及正常卵巢组织中的阳性表达率分别为53.8%(21/39)、25.0%(7/28)、7.4%（2/27）、5.9%（1/17）。NR4A2蛋白在卵巢上皮性癌组织中的阳性表达率明显高于交界性卵巢上皮性肿瘤组织、良性卵巢上皮性肿瘤组织和正常卵巢组织（P均<0.05）。交界性卵巢上皮性肿瘤的阳性表达率虽然高于良性卵巢上皮性肿瘤及正常卵巢,但差异无统计学意义（P＞0.05）。良性卵巢上皮性肿瘤的阳性表达率高于正常卵巢组,但两组之间的阳性表达率差异无统计学意义（P＞0.05）。在卵巢上皮性癌组织中,NR4A2蛋白的阳性表达率随手术分期的增加而增加（P＜0.05）,但与病理分级以及有无淋巴结转移和来源无关（P＞0.05）。结论:在卵巢上皮性癌中转录因子NR4A2呈现明显高表达,且其表达水平与手术分期相关,提示NR4A2可能与卵巢癌的发生发展相关。     

Ley 抗原在卵巢上皮性肿瘤中的表达及意义

目的:探讨卵巢癌组织ley抗原的表达及其临床意义.方法:采用免疫组织化学SP法检测恶性、交界性、良性卵巢上皮肿瘤及正常卵巢组织中ley抗原的表达,并分析其与卵巢癌生物学特性之间的关系.结果:ley抗原在恶性卵巢上皮性癌中的阳性表达率为75.47%(40/53),明显高于交界性卵巢上皮性肿瘤(47.06%)及良性卵巢上皮性肿瘤(42.86%)(P均＜0.05).正常卵巢组织中未检出ley抗原的表达.晚期卵巢上皮性癌的ley抗原的阳性表达率为84.21%,明显高于早期卵巢上皮性癌(53.33%),(P＜0.05).结论:ley抗原与卵巢上皮性癌的发生、发展相关.ley抗原的表达可作为反映卵巢癌恶性潜能的一项新的指标.     

粘蛋白MUC1在卵巢浆液性肿瘤中的表达及其临床意义

目的:研究粘蛋白MUC1在卵巢浆液性肿瘤中的表达及其临床意义。方法:应用免疫组织化学SP法检测53例卵巢浆液性囊腺癌、20例交界性卵巢浆液性囊腺瘤、20例卵巢浆液性囊腺瘤、20例正常卵巢组织中MUC1的表达情况。结果:MUC1在卵巢浆液性囊腺癌中的阳性表达率为88.7%,略高于交界性浆液性囊腺瘤中的表达(70%)(P=0.1172),明显高于良性卵巢浆液性囊腺瘤(35%)及正常卵巢组织(30%)中的表达(P<0.05)。MUC1的阳性表达与卵巢浆液性囊腺癌的临床分期有关(P<0.05),与年龄、组织分级和淋巴结转移无关(P>0.05)。结论:粘蛋白MUC1在卵巢浆液性囊腺癌的发生、发展中起重要作用,MUC1可作为判断卵巢浆液性囊腺癌生物学行为和恶性潜能的参考指标。     

中期因子在卵巢上皮性肿瘤中的表达及与其临床病理特征的关系

目的探讨中期因子（midkine,MK）在卵巢上皮肿瘤中的表达及与其临床病理特征的关系。方法采用免疫组织化学法（SP法）,检测MK在卵巢良性上皮性肿瘤、交界性肿瘤和上皮性癌组织中的表达水平,同时以正常卵巢上皮组织中MK表达水平作为对照。结果正常卵巢组织中MK无表达,良性卵巢上皮性肿瘤组织中MK阳性表达率为13.3%,交界性上皮肿瘤组织为50.0%,卵巢癌组织为89.1%,差异有显著性（P〈0.05）,MK表达与肿瘤病理类型无相关性（P〉0.05）。Ⅱ～Ⅳ期患者其阳性表达率明显高于Ⅰ期患者（P〈0.05）,有淋巴结转移者MK阳性表达率显著高于无淋巴结转移者（P〈0.05）。结论上皮性卵巢癌组织中MK表达增强,MK可作为1种有价值的肿瘤标志物。     

MUC1黏蛋白在卵巢癌中的表达

[目的]研究MUC1黏蛋白在卵巢癌中的表达及临床意义。[方法]应用免疫组化技术检测115例卵巢癌中MUC1的表达状况。[结果]黏液性卵巢肿瘤患者MUC1水平随恶性程度的增大而表达增强，MUC1的超表达及胞质的高比率表达与卵巢癌的病理分级、FIGO分期，淋巴结转移，生存期短呈正相关趋势。[结论]MUC1的表达可作为评估卵巢上皮交界性黏液肿瘤癌变潜能及卵巢癌预后有价值的指标。     

MUC1在胰腺肿瘤中的表达及意义

目的探讨MUC1 在胰腺上皮内肿瘤、胰腺导管腺癌组织中的表达及其在胰腺癌早期诊断中的意义.方法应用免疫组化技术检测30例胰腺上皮内肿瘤（PanIN）、52例胰腺导管腺癌和10例正常胰腺组织中MUC1的表达.结果 3例PanIN1-2组织中MUC1阳性表达3/18（16.7%）,7例PanIN-3组织中MUC1阳性表达7/12（58.3%）,PanIN-3与PanIN1-2阳性表达率比较差异有显著意义（P=0.024,P〈0.05）.40例胰腺导管腺癌组织中MUC1阳性表达40/52（76.9%）, MUC1阳性表达与性别、肿块大小无关（P〉0.05）,与侵袭状况、淋巴结转移、肝转移有关（P〈0.05）;结论 MUC1可作为胰腺癌早期辅助诊断指标, 有可能成为胰腺癌免疫治疗的靶抗原.     

卵巢浆液性癌中p-Akt~（473） Ser、p53及Ki-67的表达与临床意义

目的：探讨p-Akt473Ser、p53及Ki-67蛋白在卵巢癌组织中的表达及其相互关系。方法：应用免疫组化法,检测10例正常卵巢、12例卵巢良性上皮性肿瘤、15例卵巢交界性上皮性肿瘤、60例卵巢浆液性癌中p-Akt473Ser、p53及Ki-67蛋白的表达,分析p-Akt473Ser与p53及Ki-67三者间的关系。结果：pAkt473Ser、p53及Ki-67蛋白在正常卵巢组织中的阳性蛋白率分别是10%、20%、10%;pAkt473Ser、p53及Ki-67蛋白在卵巢良性上皮性肿瘤组织中的阳性蛋白率分别是17%、25%、25%,均显著低于卵巢浆液性囊腺癌组织中的60%、67%、83%（P〈0.01）。pAkt473Ser、p53及Ki-67蛋白在交界性肿瘤组织中的阳性表达率分别为40%、60%、67%,交界性肿瘤与卵巢癌组织比较,差异无统计学意义（P〉0.05）,而与组织学分化、临床分期有关（P〈0.01）。结论：pAkt473Ser、p53及Ki-67蛋白在卵巢癌中过表达,可能共同参与卵巢癌的发生、发展。     

卵巢癌组织中HE4表达及与其临床病理因素的关系

目的探讨人附睾蛋白4（HE4）在卵巢上皮性癌组织中的表达及其与卵巢癌临床病理因素的关系。方法采用免疫组化法,检测不同卵巢组织中HE4蛋白表达水平,其中47例卵巢上皮性癌组织（以下简称卵巢癌组织）、20例正常卵巢组织、20例良性卵巢上皮性肿瘤组织。结果正常卵巢组织、上皮性良性卵巢肿瘤组织及卵巢癌组织中HE4阳性表达率分别为0（0/20）,10.0%（2/20）和74.5%（35/47）,卵巢癌组织中HE4阳性表达率分别高于正常卵巢组织和卵巢良性肿瘤组织,差异均有统计学意义（P〈0.01,P〈0.01）。正常卵巢组织与卵巢良性肿瘤组织HE4阳性表达率比较,差异无统计学意义（P〉0.05）。卵巢癌晚期组（Ⅲ/Ⅳ期）HE4阳性率[89.5%（17/19）]较早期组（Ⅰ/Ⅱ期）[57.1%（16/28）]明显增高（P〈0.05）;中、低分化组其阳性率[92.6%（25/27）]较高分化组[65.0%（13/20）]明显增高（P〈0.05）;淋巴结转移组其阳性率[72.4%（21/29）]较无淋巴结转移组[38.9%（7/18）]明显增高（P〈0.05）。HE4表达与卵巢癌患者年龄无关（P〉0.05）。结论 HE4表达与卵巢癌临床分期、细胞分化及淋巴结转移有关,HE4可作为预测卵巢癌侵袭、转移及预后的指标。     

人类组织激肽释放酶6在卵巢上皮性癌中的表达及临床意义

[目的]研究人类组织激肽释放酶（kallikrein,KLK）6蛋白在卵巢上皮性癌组织及腹膜后淋巴结中的表达,探讨其在卵巢上皮性癌中的临床意义。[方法]回顾性分析卵巢肿瘤患者的临床病理资料,采用免疫组化检测72例卵巢癌、16例卵巢交界性肿瘤、20例良性卵巢上皮性肿瘤组织KLK6蛋白的表达;并采用配对设计研究KLK6蛋白在卵巢癌患者腹膜后淋巴结中的表达．探讨KLK6在卵巢上皮性癌发生、发展中的作用。[结果]KLK6在卵巢癌及交界性卵巢肿瘤中的阳性表达分别为52．8％（38／72）、25．O％（4／16）,均显著强于良性上皮性卵巢肿瘤15．0％（3／20）f19〈0．05）。KLK6阳性表达与卵巢癌的临床分期、组织学分级及淋巴结转移有关fP〈0．05）,与组织学类型无相关性（P〉0．05）;KLK6在卵巢癌原发灶与腹膜后转移淋巴结组织中的表达呈正相关（r=8．91,P=0．003）;KLK6阳性与阴性患者的平均生存时间分别为25．9个月和49．2个月（P〈O．051。[结论]KLK6高表达可能在卵巢上皮性癌的发生发展中起潜在作用,KLK6可能与卵巢上皮性癌的浸润、转移有关,KLK6是卵巢癌的不良预后因素之一。     

MUC1和MUC16在胆囊癌中的研究进展

黏蛋白（ MUC）是由上皮细胞分泌的一类高分子化、高度糖基化的糖蛋白,广泛存在于呼吸系统、消化系统、泌尿生殖系统的黏膜上皮及其分泌的黏液中。目前研究表明,黏蛋白家族与肿瘤关系密切。其中MUC1（CA153）及MUC16（CA125）已被证实在胆管癌中异常表达,但未明确二者与胆囊癌的发生发展、侵袭转移及判断预后有密切的关系。本文通过对近年来国内外文献进行回顾性分析,对MUC1和MUC16在胆囊癌中的研究进展进行综述。     

Effect of glycosylation of a synthetic MUC1 mucin-core-related peptide on recognition by anti-mucin antibodies

Human epithelial mucins are heterogeneously glycosylated proteins associated with breast and ovarian cancer. Several peptide-reactive anti-mucin MUC1 monoclonal antibodies are used in experimental and diagnostic assays but it is not known how glycosylation of the mucin influences antibody recognition. In this report we show that increasing glycosylation of a synthetic 25-amino acid fragment of the MUC1 core protein with N-acetylgalactosamine (GalNAc) elicits different responses in its recognition by two anti-MUC1 antibodies, C595 and HMFG1. We propose that increasing glycosylation of the synthetic mucin fragment produces an alteration in the structure of the epitope which enhances binding in C595, but not in HMFG1.     

黏蛋白1多肽通过small-MUC1蛋白抑制肿瘤细胞生长

目的：探讨黏蛋白1（mucin 1,MUC1）串联重复序列多肽(简称黏蛋白1多肽,MUC1多肽)对肿瘤细胞生长抑制的作用机制。方法：MUC1多肽与多种肿瘤细胞Jurkat、Raji、U937、MCF7、SMMC7721及活化的T细胞、小鼠巨噬细胞RAW264.7共同培养,观察MUC1多肽对上述细胞生长的影响;建立BABL/c小鼠Jurkat细胞皮下移植瘤动物模型,应用MUC1多肽进行治疗;采用GST免疫沉降实验鉴定与MUC1多肽结合的肿瘤细胞表面蛋白。结果：MUC1多肽对Jurkat、Raji、U937、MCF7和SMMC7721细胞的生长均有抑制作用,对活化的T细胞和小鼠RAW264.7细胞生长无明显抑制作用。MUC1多肽对BABL/c小鼠皮下Jurkat细胞移植瘤的生长均有明显抑制作用（P<0.05）。GST免疫沉降实验显示,Jurkat 和MCF7细胞裂解上清中与MUC1多肽结合的蛋白可与两种抗MUC1串联重复序列抗体（GP1.4和HMPV）及抗胞内段抗体（Ab5）发生反应,相对分子质量大约115 000,提示可能是MUC1新的同种型,命名为small MUC1（sMUC1）。结论：MUC1多肽可通过与肿瘤细胞表面small MUC1蛋白的相互作用向细胞传导生长抑制信号     

MUC1和MUC16在胆囊癌中的表达及临床意义

目的:研究MUC1和MUC16在正常胆囊黏膜、胆囊腺瘤及胆囊癌中的表达情况,以及胆囊癌中MUC1和MUC16的表达与胆囊癌Nevin分期及组织分化程度的关系。方法 :收集因胆囊息肉行胆囊切除术病例60例、胆囊腺瘤病例60例及胆囊癌病例60例,进行MUC1和MUC16的免疫组织化学染色,结合病理图像,分析其在正常胆囊黏膜组织、胆囊腺瘤及胆囊癌中的表达情况。结果:MUC1在正常胆囊黏膜组、胆囊腺瘤组和胆囊癌组中,阳性表达率分别为6.67%、38.33%、81.67%。MUC16在正常胆囊黏膜组和胆囊腺瘤组中,无阳性表达。在胆囊癌组中,阳性表达率为36.67%。MUC1和MUC16在Nevin分期 I期组、II期组、III期及III期以上组中,阳性表达率分别为62.50%、80.00%、95.83%和18.75%、30.00%、54.17%。MUC1和MUC16在高分化组、中分化组、低分化组中阳性表达率分别为60.00%、78.95%、96.15%和13.33%、26.32%、57.69%。结论:MUC1和MUC16的阳性表达在胆囊癌的发生发展中起着重要作用,MUC1和MUC16的阳性表达促进胆囊癌的发生发展。MUC1和MUC16作为一种胆囊癌的肿瘤标志物,并且预示胆囊癌的恶性程度及浸润程度。     

Immune responses to the MUC1 mucin

MUC1 mucins are highly glycosylated glycoproteins expressed on the luminal surfaces of glandular epithelia. In breast and ovarian carcinomas, their expression is frequently upregulated and they may be secreted into the circulation of cancer patients. Early studies aimed at the production of anti-MUC1 monoclonal antibodies revealed that MUC1 was a potent immunogen in mice with many monoclonal antibodies raised defining epitopes within the protein core of MUC1. The immunogenicity of MUC1 has now been extended to human studies and it is apparent that patients with breast and ovarian malignant disease are able to mount immune responses against MUC1. These findings provide information on the mechanisms involved in the recognition of MUC1 expressing tumours. The utilisation of MUC1 related immunogens to stimulate immune responses to tumours could lead to the improved management of patients and the development of new immunotherapeutic strategies aimed at the eradication of MUC1 mucin expressing cancers. These studies were supported by the Cancer Research Campaign by the award of Project Grant Number SP2168/0101     

Upregulated expression of complement inhibitory proteins on bladder cancer cells and anti-MUC1 antibody immune selection

Membrane complement inhibitors (CD46, CD55 and CD59) are upregulated in some human cancers indicating that they play a role in immune evasion. We investigated complement inhibitor expression in bladder cancer and examined the hypothesis that selective pressure of an antibody response (anti-MUC1) results in the upregulated expression of complement inhibitors on tumor cells. Paired samples of tumor and normal tissue from 22 bladder cancer patients were analyzed for expression of MUC1, CD46, CD55 and CD59, and matched serum samples analyzed for anti-MUC1 IgM and IgG levels. Relationships between anti-MUC1 antibody levels and complement inhibitor expression were investigated. MUC1 mRNA was upregulated in 86% of tumor samples. CD46 was upregulated in 77%, CD55 in 55% and CD59 in 59% of tumors. Low titer anti-MUC1 IgM was detected in normal human sera, but was elevated in 41% of the bladder cancer patients. Anti-MUC1 IgG was virtually absent from normal sera, but present in 32% of the cancer patients. There was a direct relationship between anti-MUC1 antibody titer and expression level of complement inhibitors. Analysis of the correlation of each antibody with the expression of each complement inhibitor by Spearman's rank test revealed a strong correlation between both anti-MUC1 IgM and IgG levels and increased expression of CD46 and CD55, and combined anti-MUC1 IgM/IgG levels correlated with increased expression of all 3 complement inhibitors. In conclusion, the data demonstrate upregulated complement inhibitor expression and the presence of an anti-MUC1 antibody response in bladder cancer patients and support the hypothesis of antibody-mediated immune selection.     

Induction of IgG antibodies to MUC1 and survival in patients with epithelial ovarian cancer

We investigated whether epithelial ovarian cancer patients participating in a randomized phase III trial comparing single intraperitoneal (IP) administration of yttrium-90-labeled murine HMFG1 ((90)Y-muHMFG1) plus standard treatment (AT) vs. standard treatment (ST) alone developed IgG ab to MUC1 that had an impact on disease outcome. Serial serum samples from 208 patients in the AT and 199 patients in the ST arm were tested for IgG ab to MUC1 (anti-MUC1 IgG). Anti-MUC1 IgG at weeks 4, 8 and 12 ranked higher in the AT than in the ST arm (p < 0.001). The median (range) area under the curve (AUC) of anti-MUC1 IgG for weeks 1 to 12 was 5.53 (1.51-39.51) and 3.92 (1.17-68.74) for the AT and ST arm, respectively (p < 0.001). An anti-MUC1 IgG AUC > 13 was associated with a benefit in overall survival (OS) and disease-free survival (DFS) in the AT arm in univariate (p = 0.043 and 0.036, respectively), but not in multivariate analysis (Cox proportional hazards regression model). Kaplan-Meier analysis showed a benefit in OS and DFS in patients with an anti-MUC1 IgG AUC > 13 in the AT arm (p = 0.043 and 0.036, respectively), but not in the ST arm. A single IP injection with muHMFG1 did not lead to a survival benefit in the randomized trial, but it induced ab to MUC1 that were associated with an improved disease outcome in patients with highest levels of anti-MUC1 IgG. Immunotherapy against MUC1 could be effective in the treatment of epithelial ovarian cancer.     

Tissue and Serum MUC1 Mucin Detection in Breast Cancer Patients

Tumor MUC1 expression as well as levels of MUC1, MUC1 circulating immune complexes (MUC1-CIC) and free antibodies against MUC1 (IgG and IgM-MUC1) were evaluated in 70 breast cancer patients with different stages of disease. Controls included: 135 serum samples from healthy women, normal mammary tissue samples (n=7) and benign breast disease specimens (n=6). In all assays, pre- and post-vaccination serum samples from breast cancer patients belonging to a vaccination protocol developed at the Memorial Sloan Kettering Cancer Center (New York, USA) were included as controls. Serum MUC1 was measured through Cancer Associated Serum Antigen test and CA15-3 test. Employing ELISA, MUC1-CIC-IgG/M were measured with either C595 or SM3 monoclonal antibodies (MAb) as catchers and also free antibodies against MUC1 (IgG and IgM) using 100mer peptide as catcher. Employing multivariate statistical analysis, results were correlated with age, tumor type, stage of disease and grade of differentiation. By quantitative immunohistochemistry using three anti-MUC1 core protein MAbs (C595, HMFG2 and SM3), tumor MUC1 was detected in 60/70 (86%) breast cancer specimens which reacted with at least one of these MAbs. High MUC1 serum levels were detected in 14/67 (21%); IgG and IgM anti-MUC1 antibodies were found elevated in 32 and 14%, respectively, while IgG-MUC1-CIC-measured with C595 in 42% and IgM-MUC1-CIC in 54%; finally, SM3 was positive in 43 and 18%, respectively. Results of these studies demonstrate that in a group of breast cancer patients, MUC1 was detected both in tissue specimens as well as free in serum samples; furthermore, MUC1 can also circulate complexed with IgG and IgM antibodies; thus an accurate measurement should include free and complexed forms. On the other hand, immunohistochemical studies on breast cancer tissues may contribute to reveal different MUC1 glycoforms.     

MUC1和MUC2 mRNA在不同肿瘤组织的表达及其意义

目的：检测ＭＵＣ１和ＭＵＣ２ｍＲＮＡ在没组织的表达差异，研究ＭＵＣ１和ＭＵＣ２在肿瘤诊断和免疫治疗中的意义。方法：采用了Ｄｏｔ Ｂｌｏｔ方法检测了６０例不同肿瘤组织和正常组织的ｍＲＮＡ水平。结果：ＭＵＣ１和ＭＵＣ２在吕，特别是乳腺癌和胃癌中表达明显增强，在正常组织和腺癌低度表达。ＭＵＣ１与乳腺癌的 蛤发级及病理类型明显相关，ＭＵＣ２与胃癌的病理类型明显相关。结论：ＭＵＣ１和ＭＵＣ２对乳腺癌和胃癌诊