MUC1 expression in plasmacytoma

Plasmacytoma (Pm) is a plasma cell (PC) neoplasia consisting of PCs and some of them show progression to multiple myeloma. But there is no clear indicators predicting this progression. In this study, MUC1 expression was evaluated in Pm cases to determine the predictive value and was compared with histopathologic grade which is known to be a prognostic indicator in Pm. Nine of 31 cases with Pm showed MUC1 expression. Only two of the 18 cases with mature morphology showed MUC1 expression while seven of 13 cases with immature morphology showed MUC1 expression and this was statistically significant (P<0.006). Additionally, four of 11 cases with BM involvement showed MUC1 expression while five of 20 cases without BM involvement showed MUC1 expression. There was a trend MUC1 expression with BM involvement but there was not statistically significant association between MUC1 expression and BM involvement. We found that MUC1 expression is associated with immature morphology which is an important prognostic indicator in Pm and by analogy MUC1 expression may be an additional prognostic indicator in patients with Pm.     

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。     

MUC1、MUC2及MUC5AC在大肠黏液腺癌组织中的表达及意义

目的探讨黏蛋白MUC1、MUC2和MUC5AC在大肠黏液腺癌组织中的表达及意义。方法采用免疫组织化学法的SP法,检测40例大肠黏液腺癌组织中黏蛋白MUC1、MUC2和MUC5AC的表达。结果大肠黏液腺癌组织中MUC1、MUC2和MUC5AC的阳性表达率分别为55.0%、82.5%和77.5%。大肠黏液腺癌组织中MUC1、MUC2及MUC5AC的表达与肿瘤大小及分化程度无关(P>0.05),MUC1表达与浸润深度、淋巴结转移、Dukes分期呈负相关,而MUC2、MUC5AC表达与浸润深度、淋巴结转移、Dukes分期呈正相关(P<0.05)。结论MUC1、MUC2和MUC5AC的表达可预示大肠黏液腺癌的浸润转移潜能。     

Expression of MUC1, MUC2 and oligosaccharide epitopes in breast cancer: prognostic significance of a sialylated MUC1 epitope

MUC1 represents a promising marker in breast cancer. However, due to the structural complexity of the MUC1 glycoprotein, multiple epitopes can be detected by monoclonal antibodies. This fact may be responsible for the contradictory results of previous investigations regarding the clinical and prognostic relevance of MUC1 expression in breast cancer. Therefore, we tried to evaluate the role of different glycosylated and non-glycoslyated MUC1 epitopes as well as other mucin-associated peptides (MUC2) and carbohydrates (Thomsen-Friedenreich antigen, sialyl-Lewisa, sialyl-Lewisx) as predictors of the clinical course and prognosis in mammary carcinomas. An immunohistochemical study applying numerous monoclonal antibodies (mabs) was performed to characterize the expression of a selected panel of MUC1 epitopes, and of MUC2, Thomsen-Friedenreich antigen, sialyl-Lewisa, and sialyl-Lewisx in a series of 140 patients with breast cancer. The results were correlated with clinicopathological variables as well as overall survival. Generally, more than 90% of the mammary cancers, were strongly stained with the MUC1-specific mabs. Especially ductal and lobular carcinomas were strongly MUC1- and sialyl Lewisa-positive, whereas MUC2 binding was significantly elevated in mucinous neoplasms. Associations between the immunoreactivity of any mab under study and tumor progression as reflected by pTNM staging could not be observed. However, expression of the sialylated MUC1 epitope detected by mab MY1.E12 was revealed as a favourable independent prognostic factor. These results confirm that MUC1 is generally strongly expressed in mammary carcinomas. As an exception, mucinous carcinomas are significantly less MUC1 reactive, but strongly express MUC2. Our data suggest that only the presence of a sialylated short-chain MUC1 glycoform is associated with a better prognosis, whereas the other molecules under study are not correlated with the course of disease and survival probability.     

Expression of MUC1, MUC2, MUC3 and MUC4 mucin mrnas in human pancreatic and intestinal tumor cell lines

We examined the steady-state expression levels of mRNA for the MUC1, MUC2, MUC3 and MUC4 gene products in 12 pancreatic tumor cell lines, 6 colon tumor cell lines, and one ileocecal tumor cell line. The results showed that 10 of 12 pancreatic tumor cell lines expressed MUCI mRNA and that 7 of these 12 lines also expressed relatively high levels of MUC4 mRNA. In contrast, MUC2 mRNA was expressed at only low levels and MUC3 was not detected in the pancreatic tumor cell lines. All 7 intestinal tumor cell lines examined expressed MUC2, and 5 of 7 expressed MUC3; however only one expressed significant levels of MUCI and 2 expressed low levels of M0C4 mRNA. This report of high levels of MUC4 mRNA expression by pancreatic tumor cells raises the possibility that mucin carbohydrate epitopes defined by antibodies such as DuPan 2 may be expressed on a second mucin core protein produced by pancreatic tumor cells. © 1994 Wiley-Liss, Inc.     

T cell suppression as a mechanism for tolerance to MUC1 antigen in MUC1 transgenic mice

C57BL/6 mice transgenic for human MUC1 (MUC1.Tg) have been developed to study immunologic responsiveness to the human MUC1 tumor-associated antigen. In the present studies, MUC1.Tg mice were immunized with purified human MUC1 antigen and irradiated MUC1-positive (MC38/MUC1) tumor cells. Immunization with MUC1 antigen was associated with induction of an anti-MUC1 antibody response and no detectable cytotoxic T cell reactivity. Similar findings were obtained after immunization with irradiated MC38/MUCl tumor cells. The results also demonstrate that immunization of MUC1.Tg mice with MUCl is associated with decreased levels of CD8⁺ T cells. In addition, expression of T cell receptors and CD28 were down-regulated on CD8⁺ T cells as a consequence of MUC1 immunization. These findings support a role for T cell suppression in tolerance to MUC1 antigen in MUC1.Tg mice.     

MUC1, MUC2, MUC5AC, and MUC6 expressions in gastric carcinomas: their roles as prognostic indicators.

BACKGROUND: Although mucin expressions appear to be correlated with prognoses in patients with various cancers, several studies have reported conflicting and inconclusive results on the prognostic significance of mucin expression in gastric carcinomas. METHODS: To clarify the correlations between clinicopathologic profiles and the patients' survival, the expression of MUC1, MUC2, MUC5AC, MUC6 mucins and the p53 protein were evaluated immunohistochemically in 300 consecutive gastric carcinomas using the tissue-array method. In addition, 59 gastric adenomas and 57 adenoma-associated carcinomas were investigated. RESULTS: MUC1 was expressed in 2 (3.4%) cases of gastric adenoma, and MUC2 in 19 (32.2%) cases of gastric adenoma, out of a total of 59 lesions. In consecutive gastric carcinomas, 24.3% of gastric carcinomas expressed MUC1, 27.3% expressed MUC2, 38.0% expressed MUC5AC and 12.7% expressed MUC6. The rate of MUC1 expression in gastric carcinomas was significantly higher than in associated gastric adenomas (P < 0.01). The patients with MUC1-positive carcinomas showed significantly poorer survival than those with MUC1-negative carcinomas. On the other hand, MUC2, MUC5AC and MUC6 expressions were not significantly associated with patient survival. Interestingly, combined evaluation revealed that the group with the MUC1-negative plus p53-negative expression pattern showed a better prognosis than the remaining cases. In contrast, the group with the MUC2-negative plus p53-positive pattern showed a worse prognosis. CONCLUSIONS: Mucin expression is altered in gastric adenoma and carcinoma, and MUC1 mucin expression is significantly associated with poorer outcome in gastric carcinomas. A MUC1-negative plus p53-negative pattern or a MUC2-negative plus p53-positive pattern may predict outcome in patients with gastric carcinomas.     

MUC1在泌尿系肿瘤的相关研究进展

MUC1是一种高相对分子质量糖蛋白,属于黏蛋白家族成员,正常情况下存在于许多人上皮细胞膜的腺腔面,具有多种功能,其核心肽由胞外段、跨膜段和胞内段组成。短的跨膜段和胞内段在不同种属间的结构是高度保守的,长的胞外段含有20~125个连续重复序列,连续重复序列由20个氨基酸组成,富含丝氨酸、苏氨酸和脯氨酸残基。在多种肿瘤组织中,MUC1异常表达和异常糖基化。虽然,在泌尿系肿瘤,如膀胱癌、肾癌、前列腺癌,其确切功能尚不清楚,但MUC1可作为肿瘤标志物和靶点应用于放免诊断和治疗,MUC1同这些肿瘤的浸润、转移和预后也密切相关。其在泌尿系肿瘤中特征性变化具有一定的临床应用价值。     

粘蛋白MUC1和MUC2在胃癌组织中的表达及其预后意义

目的 :探讨粘蛋白MUC1和MUC2在胃癌组织中的表达及意义。方法 :采用免疫组织化学法的SP法检测 86例胃癌组织及 2 0例人正常胃粘膜中的MUC1和MUC2的表达。结果 :在正常胃粘膜中MUC1阳性表达率为 10 0 % ,而MUC2无阳性表达。在胃癌组织中MUC1和MUC2的表达率分别为 5 8 14 %和 6 3 95 %。胃癌组织中MUC1和MUC2的表达与肿瘤大小、浸润深度及分化程度无关 (P >0 0 5 ) ,但Ⅰ～Ⅱ期、淋巴结无转移组MUC1的表达明显比Ⅲ～Ⅳ期、淋巴结转移组低 ,而MUC2表达明显增高 (P <0 0 1)。Kaplan Meier分析发现MUC1高表达和MUC2低表达患者的生存时间明显低于MUC1低表达和MUC2高表达患者 (P <0 0 1)。结论 :MUC1和MUC2可预示胃癌的转移潜能 ,两者联合表达可作为评估预后的参考指标。     

Expression of MUC1 and MUC2 mucin gene products in human ovarian carcinomas

BACKGROUND: Aberrations in expression of mucin glycoproteins have been observed during malignant transformation of human ovarian epithelium. To date, several secretory mucin genes designated the MUC gene family have been identified, of which MUC1 encodes a mammary-type and MUC2 an intestinal-type epithelial mucin. However, information on the expression and potential value of MUC1 and MUC2 mucins in ovarian cancer is limited. METHODS: This study investigated immunohistochemical expressions of MUC1 and MUC2 mucins in 23 benign and 45 malignant human ovarian tumors to assess their clinicopathological relevance. RESULTS: All benign serous tumors and also associated normal-appearing epithelia expressed MUC1 mucin on the cell surfaces. Benign mucinous tumors occasionally expressed MUC1 and MUC2 mucins. Most serous carcinomas (19/21; 90%) expressed MUC1 but not MUC2 mucin. Of the 16 mucinous carcinomas, 10 (62%) and five (31%) expressed MUC1 and MUC2 mucins, respectively. Four of the five clear cell and the three endometroid type carcinomas expressed MUC-1 but not MUC-2 mucin. A significant association was found between a high expression of MUC1 and histological grade (P = 0.005) and also disease stage (P = 0.001). CONCLUSION: These results suggest that a high expression of MUC1 may contribute to a poor prognosis in ovarian carcinoma.     

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。     

MUC1 and MUC2 expression in pancreatic ductal carcinoma obtained by fine-needle aspiration

BACKGROUND: Mucins are high molecular weight glycoproteins that are produced by various epithelial cells including those found in the pancreas. MUC1 and MUC2 are two well characterized mucin antigens. The objective of the current study was to examine the pattern of phenotypic expression of MUC1 and MUC2 in pancreatic lesions obtained by fine-needle aspiration biopsy (FNA) and to determine the utility of MUC1 and MUC2 as markers for pancreatic ductal carcinoma. METHODS: Thirty-nine cell blocks of pancreatic FNA obtained under endoscopic ultrasound guidance were retrieved from the archives and immunostained with a monoclonal antibody directed against MUC1 and MUC2. These cell blocks were taken from 39 patients (16 females and 23 males) who had a median age of 64 years. Eleven FNAs were taken from patients with reactive/inflammatory conditions. The remaining 28 FNAs included 24 ductal carcinomas, 2 neuroendocrine tumors, 1 lymphoma sample, and 1 sarcoma sample. The presence of immunoreactivity, irrespective of the level of intensity or the percentage of cells, was considered as positive for MUC1 and MUC2 expression. Follow-up included correlation with pathology materials obtained at surgery and review of medical records. RESULTS: Twenty-three of 24 pancreatic ductal carcinomas (96%) demonstrated positive staining with MUC1. Twenty-one positive cases demonstrated either apical or diffuse membranous staining with variable cytoplasmic staining. The remaining two positive cases showed only cytoplasmic staining. One of the 11 cases of chronic pancreatitis and benign conditions demonstrated weak apical membranous MUC1 staining in the acinic cells. The difference between the two groups was statistically significant (P < 0.001, using the Fisher exact test). Three pancreatic ductal carcinomas and one chronic pancreatitis specimen demonstrated cytoplasmic staining with MUC2; the difference between the two groups was not found to be statistically significant. None of the nonductal neoplasms demonstrated expression of either MUC1 or MUC2. The sensitivity and specificity of MUC1 as a marker for pancreatic ductal carcinomas were 96% and 94%, respectively. CONCLUSIONS: MUC1 is overexpressed in pancreatic ductal carcinoma with a predominantly membranous and variable cytoplasmic staining pattern. The results of the current study suggest that the phenotypic expression of MUC1 can be used as an ancillary marker for diagnosing pancreatic ductal carcinoma in cytologic preparations. Conversely, MUC2 does not appear to be a useful marker for recognizing pancreatic ductal carcinoma in FNA specimens.     

Polymorphisms in MUC1, MUC2, MUC5B and MUC6 genes are not associated with the risk of chronic atrophic gastritis

Mucins represent major components of the mucous layer in the stomach, protecting the underlying epithelium from acid, mechanical trauma, proteases and pathogenic bacteria. Previous studies have shown an association of neoplastic transformation in the stomach with aberrant mucin levels, suggesting a potential role of genetic variation in mucin genes in the development of gastric cancer (GC). We assessed the association of genetic variation in candidate single nucleotide polymorphisms (SNPs) in mucin genes with the risk of chronic atrophic gastritis (CAG), a well-established precursor of GC in the German population-based ESTHER study. We genotyped MUC1 T31T, MUC2 L58P, MUC2 V116M, MUC5B E34G, MUC5B R51W, MUC5B rs2014486 (intronic) and MUC6 V619M for 533 serologically defined CAG cases and 1054 age- and sex-matched controls. None of the analysed SNPs was associated with CAG. However, large studies are needed to disclose or exclude potential weak associations of these SNPs with CAG risk.     

粘蛋白MUC1、MUC2在大肠腺癌中的表达及其临床意义

 目的　探讨粘蛋白MUC1和MUC2在大肠腺癌及大肠腺瘤中的表达及其与临床各个病理参数之间的关系。方法　应用免疫组织化学方法对 6 0例大肠腺癌和 2 0例大肠腺瘤进行粘蛋白MUC1、MUC2检测。结果　 2 0例大肠腺瘤及 6 0例大肠腺癌中 ,粘蛋白MUC1阳性表达率分别为 10 %、4 6 .7% ;粘蛋白MUC2阳性表达率分别为 10 0 %、5 8.3%。大肠腺癌中粘蛋白MUC1的表达与肿瘤的分化程度呈负相关 ,与浸润深度、淋巴结转移、Dukes分期及生存期呈正相关。MUC2的表达与分化程度无关 ,而与浸润深度、淋巴结转移、Dukes分期及生存期均呈负相关。结论　MUC1的上调表达或MUC2的下调表达可能参与了大肠腺癌的发生、发展、浸润及转移 ,对临床上判断预后具有较大的意义。     

结肠直肠癌组织中粘蛋白MUC1和MUC2的表达及临床意义

背景与目的：粘蛋白MUC1的表达上调或MUC2的表达下调可能参与了肿瘤的发生,而MUC1和MUC2的表达中国人结肠直肠癌发生发展的关系未见报道。本研究的目的是探讨结肠直肠癌组织中粘蛋白MUC1和MUC2的表达与不同的临床病理参数间的关系及其临床意义。方法：采用免疫组化方法检测126例结肠直肠癌和20例正常结肠直肠粘膜中粘蛋白MUC1和MUC2的表达。结果：20例正常结肠直肠粘膜中粘蛋白MUC1和MUC2的表达阳性率分别为0和100％,而126例结肠直肠癌中粘蛋白MUC1和MUC2的阳性表达率分别为42．1％和36．5％（P＜0．01）;结肠直肠癌中粘蛋白MUC1的表达与肿瘤的浸润深度、淋巴结转移和Dukes分期呈正相关（P＜0．05）,与肿瘤的分化程度呈负相关（P＜0．01）;粘蛋白MUC2在结肠直肠癌中的表达与肿瘤的浸润浓度、淋巴结转移和Dukes分期密切相关（P＜0．05）,而与肿瘤的分化程度无关（P＞0．05）。结论：粘蛋白MUC1表达上调或MUC2表达下调可能参与了结肠直肠癌的发生发展,检测结肠直肠癌中粘蛋白MUC1和MUC2的表达可间接反映肿瘤的预后。     

Role of MUC1 and MUC5AC expressions as prognostic indicators in gastric carcinomas

BACKGROUND AND OBJECTIVES: The aim of this study is to clarify the relationship between the expression of MUC1 and MUC5AC mucins and the clinicopathological features in human gastric carcinomas using the mouse monoclonal antibodies VU-4H5 and Clone 45M1, respectively. Furthermore, the possibility of using phenotypes (MUC1+/MUC5AC+, MUC1+/MUC5AC-, MUC1-/MUC5AC-, MUC1-/MUC5AC+) to predict prognosis of the patients is evaluated. METHODS: Formalin-fixed, paraffin wax-embedded tissues from 76 cases of gastric cancer were examined for the expression of MUC1 and MUC5AC mucin antigens immunohistochemically using the avidin-biotin-peroxidase method. RESULTS: Of the 76 cases, MUC1 and MUC5AC immunoreactivities were observed in 49 (64.5%) and in 32 (42.1%) of gastric carcinoma tissues, respectively. MUC1 expression was significantly correlated to the depth of invasion, lymph node metastasis, peritoneal dissemination, and tumor stage. On the other hand, MUC5AC was inversely associated with depth of invasion, lymph node metastasis, liver metastasis, and tumor stage. Multivariate analyses indicated that tumor stage and MUC1 mucin expression were independently correlated with overall survival. The patients with MUC1+/MUC5AC- antigen staining in carcinoma tissues showed the lowest survival rate among four phenotypes. In contrast, the patients with MUC1-/MUC5AC+ antigen staining in carcinoma tissues showed the highest survival rate. CONCLUSIONS: Altogether these data suggest that combined evaluation of MUC1 and MUC5AC mucin staining may be clinically helpful to predict outcome in patients with gastric cancer.     

Racial differences in the prognostic usefulness of MUC1 and MUC2 in colorectal adenocarcinomas.

There is a need for new prognostic parameters that could add insights into the aggressiveness of tumors. Because the expression of two well-characterized mucin antigens, MUC1 and MUC2, in colorectal adenocarcinomas (CRCs) has been correlated with the aggressiveness of CRCs, we evaluated the prognostic value of the expression of MUC1 and MUC2 in CRCs collected from African-American and Caucasian patients. Expression of MUC1 and MUC2 was evaluated by immunohistochemistry in 166 archival CRC specimens collected from 58 African-American and 108 Caucasian patients that had been analyzed previously for nuclear accumulation of p53 (p53nac). Univariate Kaplan-Meier and multivariate Cox proportional hazards models were used to determine the prognostic significance of expression of MUC1 and MUC2 in these CRCs. MUC1 expression was more frequent in advanced stage CRCs, whereas MUC2 expression was higher in the mucinous type of CRCs. Although similar proportions of CRCs from African-Americans and Caucasians expressed MUC1 and MUC2, the MUC1 expression was found to be an indicator of high risk of death from CRC in Caucasians (hazard ratio, 2.03; P = 0.038) but not in African-Americans. Furthermore, Caucasians with CRCs exhibiting concomitant expression of MUC1 and p53nac demonstrated the lowest probability of overall survival (log rank test, P = 0.004). No prognostic value was found for MUC2 alone or in combination with p53nac in either group of patients. Expression of MUC1 in CRCs is a valuable indicator of poor prognosis in Caucasian patients. Additionally, combined evaluation of MUC1 and p53nac increases the ability to identify Caucasian patients with aggressive subtypes of CRC and may be useful in selecting or in developing novel therapeutic regimes.     

Expression and localization of MUC1, MUC2, MUC5AC and small intestinal mucin antigen in pancreatic tumors

Alterations in the expression of mucin family members play an important role as well as alterations in oncogenes and onco-suppressor genes in carcinogenesis and progression of pancreatic cancer. We analyzed the expression and localization of MUC1, MUC2, MUC5AC and small intestinal mucin antigen (SIMA) in pancreatic tumors. MUC1 expression was observed in almost all samples, whereas MUC2 expression was not. MUC5AC expression was observed in 73.9% of the cancerous regions, 48.7% of the dysplastic regions and 72.0% of the hyperplastic regions but not in the normal pancreatic duct. SIMA expression was observed in 45.7% of cancerous regions, 17.9% of the dysplastic regions and 8.0% of the hyperplastic regions. Furthermore, stromal expression of MUC1, MUC5AC and SIMA was observed in 37.0%, 60.9% and 26.1% of the cancerous regions, respectively. Stromal expression of these mucins was not observed in the hyperplastic regions and normal pancreatic duct and was observed in only two dysplastic regions. The survival of pancreatic cancer patients with stromal expression of MUC1 or SIMA was worse than that of other patients (P=0.04). In conclusion, the localization of mucin expression, especially stromal expression of MUC1 or SIMA, might be a prognostic factor for patients with pancreatic cancer.     

MUC1, a therapeutic target in oncology

MUC1 is a large, highly glycosylated protein expressed on the apical membrane of many epithelial cells. With other members of the mucin family it contributes to the protection and function of mucosal cells. The intracellular part of the protein may also participate in signal transduction pathway, through multiple interactions with intracellular proteins. Overexpression of MUC1 is frequently observed in the majority of epithelial cancers and even in some haematological malignancies. In tumor cells, MUC1 loses apical distribution and is hypoglycosylated. These cancer-associated changes render it antigenic and make it an attractive target for a specific cancer immunotherapy. Several MUC1-based therapeutic cancer vaccines are currently under clinical investigation.