卵巢浆液性和黏液性肿瘤MUC1、MUC2的表达及其意义

目的探讨卵巢浆液性和黏液性肿瘤中黏蛋白MUC1、MUC2的表达与临床病理特征的相关性。方法免疫组化S—P法检测90例卵巢浆液性和黏液性肿瘤的黏蛋白MUC1、MUC2的表达,并对其中50例恶性病例作生存分析。结果（1）交界性与恶性卵巢肿瘤中黏蛋白MUC1的表达阳性率明显高于良性肿瘤,差异有显著性（P〈0．001）;黏蛋白MUC1与WHO病理分级、FIGO临床分期、大网膜转移显著相关（P〈0．05）。（2）黏蛋白MUC2与组织学类型、WHO病理分级相关（P〈0．05）。（3）黏蛋白MUC1与MUC2呈负相关（P〈0．05）。（4）对50例恶性浆液性和黏液性肿瘤进行的生存分析中,单因素分析显示：WHO病理分级、FIGO临床分期、大网膜转移、MUC1表达程度与预后相关（P〈0．05）,而多因素分析中只有FIGO临床分期、MUC1表达程度具有独立的预后意义（P〈0．05）,Kaplan—Meier生存曲线分析显示,Ⅲ、Ⅳ期较Ⅰ、Ⅱ期生存率差异有显著（P〈0．01）,MUC1阳性组和阴性组生存率差异有显著性（P〈0．01）。结论黏蛋白MUC1、MUC2与恶性卵巢浆液性和黏液性肿瘤的浸润、转移相关,Ⅲ、Ⅳ期肿瘤、MUC1强表达可作为恶性卵巢浆液性和黏液性肿瘤预后不良的可行性指标。     

MUC1/Y基因在胃肠道肿瘤中的表达及诱导抗肿瘤免疫

目的 研究MUC1／Y基因异常表达在消化道肿瘤中的临床意义；构建MUC1／YcDNA全长载体，修饰树突状细胞(DC)诱导杀伤细胞治疗消化道肿瘤。方法 采用RT-PCR方法检测标本中MUC1／YmRNA表达。选取8例HLA-A2^ 消化道肿瘤患者，体外诱导DC，以构建的MUCl／YcDNA真核表达载体pcDNA3．1-MUC1／Y修饰DC诱导CTL。通过检测对靶细胞SW620和Raji的杀伤作用和诱导靶细胞凋亡的能力来评价抗肿瘤免疫反应。结果 93．88％肿瘤组织表达较高水平的MUC1／Y。分析表明：消化道肿瘤中MUC1／YmRNA表达与组织学分型、肿瘤生长方式、浸润程度及TNM临床分期有关；与性别、肿瘤发生部位及分化程度无关。pcDNA3．1-MUC1／Y修饰DC诱导的CTL对特异性靶细胞的杀伤活性显著高于对照组，并能有效诱导靶细胞凋亡。结论 MUC1／YmRNA表达在消化道肿瘤组织具有重要意义；经pcDNA3．1-MUC1／Y修饰的DC可有效诱导特异性抗肿瘤免疫应答。     

非小细胞肺癌中E-cadherin、MUC1及PINCH的表达及其临床意义

目的:分析与细胞黏附相关的E-cadherin、MUC1及PINCH在非小细胞肺癌(NSCLC)中表达水平,并探讨三者之间的相关性,探寻NSCLC病变进展更具代表性的指标。方法:通过免疫组化法检测70例非小细胞肺癌患者E-cadherin、MUC1及PINCH的表达情况并结合临床分期及有无淋巴结转移进行统计学分析,并探讨三者之间的相关性。结果:NSCLC肿瘤组织中E-cadherin、MUC1及PINCH蛋白的阳性表达率分别是25. 7%、57. 1%和62. 9%,与对照组相比差异具有统计学意义(P0. 01); E-cadherin阳性表达率随着临床分期的升高而下降(P0. 01),而MUC1和PINCH阳性表达率随着分期的升高而升高(P0. 01);有淋巴结转移的肺癌组织中E-cadherin阳性表达率较无淋巴结转移者显著降低(P0. 05),而有淋巴结转移的肺癌组织中MUC1和PINCH阳性表达率较无淋巴结转移者显著升高(P0. 05); NSCLC肿瘤组织中MUC1与PINCH的表达水平呈正相关(r=0. 589,P0. 01),MUC1、PINCH的表达水平与E-cadherin呈负相关(相关系数r值分别为-0. 562,-0. 415,P值均0. 01)。结论:E-cadherin,MUC1及PINCH三者可能互相联系共同影响细胞间的黏附性进而促进NSCLC的进展;同时检测三者在NSCLC癌组织中的表达,对于探寻NSCLC病变进展更具代表性的指标可能有重要意义。     

子宫内膜样腺癌MUC1表达及其与ER、PR表达的相关性

目的 探讨跨膜型黏蛋白1(Mucin 1,MUC1)在子宫内膜样腺癌中的表达及其与ER、PR的相关性.方法 采用免疫组化EnVision法检测56例子宫内膜样腺癌、28例不典型增生性子宫内膜及18例增生性子宫内膜组织中MUC1蛋白的表达,同时检测子宫内膜样腺癌组织中ERα、PR的表达.结果 (1)在增生性子宫内膜、不典型增生性子宫内膜和子宫内膜样腺癌中,MUC1蛋白异质表达率分别为27.8%、71.4%和80.4%,差异有显著性(P=0.000).(2)子宫内膜样腺癌中,随着患者绝经的发生、组织学分级、分期的提高和肌层浸润加深,MUC1蛋白异质表达率有增加趋势(P>0.05);ERα、PR蛋白表达与组织学分级关系密切(P=0.003,P=0.008),与患者月经状态、肌层浸润、淋巴结转移及手术病理分期无关(P>0.05).(3)子宫内膜样腺癌中,MUC1蛋白表达与ERα蛋白有的负相关关系,与PR蛋白有部分呈正相关关系,但关系不密切(P>0.05).结论 子宫内膜样腺癌中MUC1蛋白异常表达率显著升高,并且与ER、PR有相互调节关系.     

大肠腺癌中Sema4D和VEGFR2的表达及意义

目的探讨Sema4D和血管内皮生长因子受体2(VEGFR2)在大肠腺癌组织中的表达及其临床意义。方法运用组织芯片和免疫组化SP法检测115例大肠腺癌组织、19例大肠腺瘤组织和12例正常大肠黏膜组织中Sema4D与VEGFR2的表达,并分析其与临床病理特征的关系。结果 Sema4D在正常大肠黏膜表达阳性率8.33%,在腺瘤和腺癌中阳性表达率为15.79%和39.13%,差异有统计学意义且与淋巴结转移、Dukes临床分期明显相关(P<0.05)。VEGFR2在正常大肠黏膜中阳性率16.67%,在腺瘤和腺癌中表达率为21.05%和51.3%,差异有统计学意义其表达与淋巴结转移、浸润程度、Dukes临床分期明显相关(P<0.05)。结论大肠腺癌中Sema4D与VEGFR2的表达可能在大肠腺癌的发生、发展中发挥重要作用。     

大肠腺癌中iNOS和COX-2的表达及意义

目的 探讨大肠腺癌中iNOS和COX-2的表达及其与大肠腺癌生物学行为的关系.方法 采用SP免疫组化方法检测78例大肠腺癌标本及33例癌旁正常肠黏膜组织中的iNOS和COX-2的表达,并对两指标表达与临床病理参数之间进行相关分析.结果 ① iNOS和COX-2在大肠腺癌中阳性率分别显著高于正常大肠黏膜阳性率(P<0.05);② iNOS、COX-2的表达与大肠癌淋巴结转移明显相关(P<0.05);③ iNOS和COX-2在大肠腺癌中的阳性表达与临床分期有关,在TNM分期中Ⅲ+Ⅳ期阳性表达率高于Ⅰ+Ⅱ期(P<0.05);④ 大肠腺癌组织中COX-2表达与iNOS表达之间存在明显相关性(P<0.05).结论 COX-2和iNOS过度表达参与了大肠腺癌的发生发展过程,并与其淋巴结转移和TNM分期有关;大肠腺癌中COX-2和iNOS的表达具有正向协同性.     

人胃、肠黏蛋白糖链在胃肿瘤中的表达

目的：探讨新制备抗人胃,肠黏蛋白糖链抗体（HGM72,HGM75,HCM14和HCM21）及抗核蛋白MUC2抗体（NCL－MUC2）在胃黏膜,化生胃黏膜及肿瘤中的表达,方法：使用LSAB试剂盒对15例胃腺瘤,136例浅表型胃腺癌（肠型77例,弥散型59例）及10例正常胃黏膜,10例化生胃黏膜进行免疫组织化学染色和组织化学染色,结果：HGM72抗原表达在正常胃窦腺和胃底腺的颈细胞胞质中,两型胃腺癌的表达明显高于胃腺瘤（P＜0．01）,两型胃腺癌之间无差异;HGM75抗原表达在胃小凹上皮细胞胞质中,在胃腺瘤和弥散型胃腺癌的表达明显高于肠型胃腺癌（P＜0．01）,HCM14抗原部分表达在化生胃黏膜的杯状细胞胞质中,在胃腺瘤的表达高于胃腺癌和化生胃黏膜（P＜0．01）;HCM21抗原均表达低下;MUC2表达在化生的杯状细胞胞质中,在胃肿瘤中无明显差异,结论：抗黏蛋白链抗体与其它染色联合使用,能更好地显示黏蛋白在胃肿瘤中的变化。     

MUC1/Y胞外段在大肠杆菌中的表达和鉴定

目的：获得MUC1／Y胞外段重组蛋白，研究其生物学功能，为肿瘤治疗提供实验依据。方法：利用RT—PCR从MCF7细胞中获得MUC1／Y胞外段编码基因，将其克隆到原核表达载体pET-32a中，并在BL21（DE3）大肠杆菌中进行表达；以亲和层析法对MUC1／Y重组蛋白进行纯化；利用纯化的MUC1／Y蛋白免疫家兔制备MUC1／Y多克隆抗体，然后对乳腺癌组织进行组化染色。结果：在大肠杆菌BL21（DE3）中成功表达了分子量为30000的Trx—MUC1／Y融合蛋白，经镍亲和层析一步纯化所获得的蛋白质纯度〉90％，用Trx-MUC1／Y融合蛋白免疫家兔获得的抗血清对乳腺癌组织的初步组化检测证明MUC1／Y融合蛋白具有很好的生物学活性。结论：成功表达并纯化了具有生物学活性的MUC1／Y胞外段重组蛋白。     

鼠与人MUC1分子同源性位点的分析

目的：分析鼠与人粘蛋白1（MUC1）的同源性位点。方法：用抗人类MUC1单克隆抗体GP1.4、CA15－3,通过细胞ELISA和Western blot鉴定鼠Lewis肺癌细胞表面MUC1分子的表达，并用蛋白分析软件分析鼠与人MUC1分子的同源性。结果：抗人类MUC1单克隆抗体GP1．4和CA15－3与Lewis肺癌细胞表面MUC1存在交叉反应；鼠与人MUC1分子约具有49．1％的同源性。结论：鼠与人MUC1分子具有一定的同源性，可用鼠Lewis肺癌细胞作荷瘤鼠研究人类MUC1肿瘤疫苗；鼠源性MUC1蛋白也可用于制备人类的肿瘤疫苗。     

ATRA联合Genistein对A549人肺腺癌细胞株MUC1表达及转移潜能的影响

目的 MUC1是一种跨膜粘蛋白,在肿瘤进展过程中起重要作用,MUC1可作为多种肿瘤预后判断的有用标记,本实验探讨了全反式维甲酸(all-trans retinoic acid,ATRA)联合三羟异黄酮(Genistein)对肺腺癌细胞MUC1蛋白、mRNA的表达及转移潜能的影响.方法 ATRA、Genistein及两者联合处理人肺腺癌细胞株A549,免疫组化法检测MUC1蛋白的表达情况,荧光定量PCR法检测MUC1 mRNA的表达,根据细胞穿过铺有Matrigel胶多孔膜的数量检测细胞侵袭力.结果 ATRA和Genistein联合处理A549肺癌细胞后,具有协同下调细胞MUC1蛋白、mRNA的表达,抑制A549细胞体外侵袭能力的作用.结论 ATRA联合Genistein可能通过协同下调MUC1蛋白及mRNA的表达,从而抑制肺癌A549细胞的转移潜能.     

Significance of MUC1 and MUC2 mucin expression in colorectal cancer.

AIMS: To compare the lineage specific distribution of MUC1 and MUC2 mucins in normal colorectal mucosa and adenocarcinoma and to identify pathological correlations. METHODS: Paraffin wax sections from 51 colorectal cancers were examined for the expression of MUC1 and MUC2, non-O-acetyl sialic acid and the carbohydrate epitopes Lex, Ley, sialosyl-Lex, sialosyl-Tn, and Tn using standard histochemical methods. RESULTS: MUC1, Lex and Ley co-localised with columnar cell secretions, whereas MUC2, mild periodic acid Schiff and sialosyl-Tn co-localised with goblet cell mucin in both normal and malignant tissues. Sialosyl-Lex and Tn were associated with both lineages. In normal tissues MUC1, Lex and Ley showed only trace expression by crypt base columnar cells. Cancers could be classified into four phenotypes (MUC2+/MUC1-, MUC2+/MUC1+, MUC2-/MUC1+, MUC2-/MUC1-). Particular phenotypes showed significant correlations with cancer type, lymph node spread and peritumoral lymphocytic infiltration and trends falling short of significance in relation to grade of differentiation and contiguous adenoma. CONCLUSIONS: Classification of colorectal cancer by means of lineage specific function may be relevant to both pathogenesis and prognosis.     

Expression of MUC5AC in colorectal carcinoma and relationship with prognosis

Overexpression and alterations in the glycosylation of gastric mucins have been described in colorectal carcinoma. The purpose of our study was to confirm aberrant expression of MUC5AC in colorectal carcinoma, to investigate relationships between clinicopathological parameters and MUC5AC expression, and to determine if MUC5AC expression may be a prognostic factor for colorectal carcinoma. Immunohistochemical staining using an antibody against MUC5AC tandem repeat epitopes was performed on colorectal tumor specimens (n = 41), their metastatic tumors in regional lymph nodes (n = 21) and normal colonic mucosa (n = 41). We also documented clinicopathological parameters such as the age and sex of the patient, location, size, Dukes stage, histological type and grade of the tumor, pre-sence and number of metastatic lymph nodes, lymphatic, venous and perineural invasion, presence of preoperative and postoperative metastatic tumors and tumor recurrence. MUC5AC was expressed in 34.1% of tumor samples, 24.4% of normal colonic mucosa samples and 19% of lymph node metastases. MUC5AC showed ectopic expression in colorectal carcinoma and was also expressed strongly in mucinous carcinoma (60%). The number of tumors that expressed MUC5AC was lower in patients older than 60 years, in rectum-localized tumors and in patients who had evidence of recurrence and/or metastasis in the postoperative period. The patients with MUC5AC-negative tumors had a lower incidence of being disease free and of overall survival. In conclusion, the patients with MUC5AC-negative tumors had poor clinicopathological parameters and showed worse survival than patients with MUC5AC-positive tumors. Absence of MUC5AC expression in tumors can be a prognostic factor for more aggressive colorectal carcinoma.     

Comparative evaluation of the prognostic value of MUC1, MUC2, sialyl-Lewis(a) and sialyl-Lewis(x) antigens in colorectal adenocarcinoma

AIMS: The significance of MUC1, MUC2 and sialylated Lewis blood group antigens as prognostic markers in colorectal adenocarcinoma was investigated in a large series of patients because previous investigations revealed inconsistent results due to unrelated tumour samples from different patient groups and methodological differences. METHODS AND RESULTS: Tissues from 243 patients with colorectal adenocarcinoma were stained immunohistochemically. MUC1 showed a strong immunoreactivity (in more than 35% of the tumour area) in 32.5%, MUC2 in 51.0%, sialyl-Lewis(x) in 67.9% and sialyl-Lewis(a) in 73.7% of the cases, respectively. MUC1 immunoreactivity displayed a significant correlation with tumour progression as reflected by advancing pTNM staging and poor differentiation. MUC2 expression was significantly stronger in mucinous adenocarcinomas. Sialyl-Lewis(x) immunostaining correlated with the extent of lymph node metastasis as well as low cytological differentiation. According to univariate and multivariate analysis (P < 0.0001) only MUC1 reactivity represented a marker of worse survival probability, opposed to the sialylated Lewis antigens that did not exert a predictive value. CONCLUSIONS: According to our data, MUC1 and sialyl-Lewis(x) immunoreactivity exhibit statistically significant correlations with established markers of tumour progression. However, only MUC1 presents as an independent prognostic factor of colorectal adenocarcinoma.     

Coexpression of MUC1 with p53 or MUC2 correlates with lymph node metastasis in colorectal carcinomas

The alteration of the mucin profile have been known to play a role in colorectal carcinogenesis. MUC1 is up-regulated and MUC2 is down-regulated in colorectalcarcinomas. Overexpression of p53 is frequently noted in colorectal carcinomas with deep invasion or lymph node metastasis. However, there have been few reports about the association between MUC1, MUC2, and p53 expression with respect to the metastatic potential. This study was aimed to investigate the relationship of MUC1, MUC2, and protein p53 expressions with clinicopathological factors in colorectal carcinomas. Expressions of MUC1, MUC2, and p53 protein were examined immunohistochemically. Of total 97 cancers, 44 (45%) were MUC1 positive, 39 (40%) were MUC2 positive and 58 (59%) showed a p53 overexpression. Coexpression of MUC1 with p53 and dual expression of MUC1 with MUC2 were associated with a higher frequency of lymph node metastasis (p<0.05). The right colon showed a higher MUC1 positivity and frequent lymph node metastasis than the left colon (p<0.05). These results suggest that the coexpression of MUC 1 with p53 or MUC2 are involved in regional lymph node metastasis in colorectal carcinomas. The high expression of MUC1 in the right colon cancer was revealed to relate with lymph node metastasis.     

MUC expression in adenosquamous carcinoma of the head and neck regions of Japanese patients: Immunohistochemical analysis

Adenosquamous carcinoma (ASC) is a rare malignant neoplasm of the head and neck regions. We elucidated the relationship between ASC and MUC molecule expression. We selected 14 cases of ASC in the head and neck, and examined them immunohistohcmically. Seven cases of tongue, 3 cases of larynx and 4 cases of hypopharynx carcinoma were selected. Nine (64.3%) of 14 cases showed lymph node metastasis at the diagnosis. Laryngeal and hypopharyngeal cases showed a higher stage. Six cases (66.7%), all of which showed lymph node metastases, died of disease. Immunohistochemical examinations showed that ASC was positive for both markers of squamous cell carcinoma and adenocarcinoma. ASC showed positivity for MUC1 (13 cases: 92.3%), MUC1core (12 cases: 85.2%) and MUC4 (12 cases: 85.7%). In rare ASC of the head and neck region, it was revealed that MUC1 and MUC4 expression might be associated with its nodal status.     

MUC1 and MUC2 mucins in flat and polypoid colorectal adenomas.

AIMS: To examine the expression of MUC1 and MUC2 apomucins and distribution of MUC phenotypes (MUC2+/ MUC-, MUC2+/MUC1+, MUC2-/ MUC1+, MUC2-/MUC1-) in colorectal tubular adenomas in order to compare the distribution of phenotypes in flat and polypoid adenomas. METHODS: Endoscopically resected specimens of 35 flat and 15 polypoid tubular adenomas measuring less than 10 mm were examined and compared for the expression of MUC1 (MUSE11) and MUC2 (CCP58) and combined MUC phenotype distribution using conventional immunohistochemistry. RESULTS: There was no significant difference between flat and polypoid adenomas in their expression of MUC1 and MUC2 and the MUC phenotype distribution when stratified by grade of histological atypia. Adenomas with low grade atypia showed more extensive MUC2 expression than MUC1 (MUC2+/MUC1-phenotype). Expression of MUC1 was more extensive in adenomas with high grade atypia and the majority displayed either MUC2+/ MUC1+ or MUC2-/MUC1+ phenotypes. CONCLUSIONS: MUC2/MUC1 phenotypes were similar in flat and polypoid adenomas when stratified by grade of atypia. High grade atypia was characterised by reduced MUC2 and increased MUC1 expression in both types of adenoma. The phenotype MUC2-/MUC1+ occurs in tubular adenomas and cannot be a specific marker for de novo colorectal cancer.     

Expression of MUC1 and MUC2 mucins and relationship with cell proliferative activity in human colorectal neoplasia

Our previous studies on MUC1 and MUC2 mucin expression in various human neoplasms have found that MUC1 expression is related with a poor outcome whereas MUC2 expression is related with a favorable outcome. In the present study, we examined the alteration of MUC1 and MUC2 antigens on malignant transformation of colorectal mucosa, and also its relationship with cell proliferative activity (Ki-67 labeling index) of neoplastic epithelial cells in 200 adenomas and 58 carcinomas. In the 200 adenomas, we analyzed a total of 400 adenomatous lesions (mild dysplasia, 200 lesions; moderate dysplasia, 153 lesions; severe dysplasia, 47 lesions). MUC1 was expressed in carcinomas (24%) and adenomas with severe dysplasia (4%), but was not expressed in adenomas with mild or moderate dysplasia. MUC2 was expressed in a significantly greater number of adenomas with mild dysplasia (72%) than in adenomas with moderate dysplasia (45%) or severe dysplasia (47%), as well as in the carcinomas (38%; P < 0.0001). The Ki-67 labeling index was significantly lower in the MUC2-positive cases than in the MUC2-negative cases in the adenomas with mild dysplasia (13.6 vs 24.2%; P < 0.0001) or moderate dysplasia (25.7 vs 44.4%; P < 0.0001), and in the carcinomas (32.5 vs 48.4%; P < 0.05). In conclusion, the data from our study indicate that increased MUC1 expression and reduced MUC2 expression may be related to malignant transformation of colorectal neoplasia. We also demonstrated that decreased MUC2 expression, which is correlated with increased Ki-67 labeling, may play an important role in the progression of colorectal adenomatous change.     

Loss of phenotypic expression is related to tumour progression in early gastric differentiated adenocarcinoma

AIMS : To evaluate the relationship between phenotypic expression and tumour progression as represented by macroscopic features, submucosal invasion and lymph node metastasis in early differentiated gastric adenocarcinoma. METHODS : One hundred and fifty-five cases of early gastric differentiated adenocarcinoma without any poorly differentiated components were studied. The mucosal and submucosal components of carcinomas and lymph node metastatic lesions were classified into four categories, gastric type (G-type), incomplete intestinal type (I-type), complete intestinal type (C-type) and unclassified type (U-type), based on the combination of the phenotypic expression of HGM (gastric foveolar epithelium), MUC 6 (gastric pyloric glands), MUC 2 (intestinal goblet cells) and CD 10 (small intestinal brush border). In addition, a new classification representing a phenotypic shift from mucosa to submucosa or from primary lesion to lymph node metastasis was established with the categories of preserved group (P-group), loss group (L-group) and acquired group (A-group). RESULTS : (1) In submucosal carcinoma, U-type was more common in the submucosa (39%) than in the mucosa (9%). (2) U-type was more common in the metastatic lesions (42%) than in the primary lesions (5%). (3) The submucosal component and lymph node metastatic lesions were classified as P-group in 48% and 43% of cases, respectively, and as L-group in 50% and 52% of cases, respectively. (4) Lymph node metastatic lesions comprising undifferentiated carcinoma were classified as L-group in 100% of cases. CONCLUSION : During the course of tumour progression, early differentiated adenocarcinoma at first tends to lose its phenotypic expression despite preserving its morphology, but subsequently morphological dedifferentiation occurs.