Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mucin glycoprotein can promote tumor-cell invasion metastasis and modulate the immune recognition of cancer. This study aimed to elucidate the clinical significance of mucin gene overexpression in lung cancer. We collected 60 lung cancer samples and paired non-tumorous lung portions of varying types and stages. Slot-blot analysis with specific anti-sense oligonucleotide probes derived from tandem repeat sequence of MUC1, -2, -3, -4, 5B and 5AC were utilized to compare the amount of mucin gene mRNA in tumor samples with that of the non-tumorous counterparts. A ratio higher than 1.5 for each specific mucin mRNA amount was considered to indicate mucin gene overexpression in tumors. Immunohistochemical staining of monoclonal antibodies against mature airway mucin (17Q2) and MUC1 mucin protein (HMFG2) were also used to analyze mucin protein. The study showed that overexpression of mucin genes frequently occurred in lung cancer (25 out of 60, 41.7%), but that there was no preferential expression of a particular mucin gene or a combination of mucin genes in these tumors. The overexpression of mucin genes and mucin protein had no correlation with tumor stage, nodal stage, histology or pathological differentiation grade. Tumors of smokers had higher MUC5B and MUC5AC mRNA expression ratios than those of non-smokers. Tumors with increased expression of mucin genes tended to be associated with post-operative relapse, especially when MUC5B and MUC5AC genes were overexpressed (p = 0.015 and 0.025, respectively). The study suggests that overexpression of novel tracheobronchial mucin genes may result in an increased likelihood of post-operative lung-cancer recurrence or metastases.
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PMID:Overexpression of MUC5 genes is associated with early post-operative metastasis in non-small-cell lung cancer. 898 Feb 47

Although the loss of sulfomucins was known as an indicator of carcinogenesis and malignant progression of colonic epithelia, it was not known whether the loss was directly related to the malignant behavior of colon carcinoma cells. We have studied the biological properties of LS174T human colon carcinoma cells before and after suppression of sulfomucin production. Incorporation of [35S]-sulfate into high molecular weight mucins decreased after carcinoma cell treatment with 1.5% dimethylsulfoxide (DMSO) for 8 days. The amounts of sulfomucin determined using a sulfomucin-specific monoclonal antibody (mAb 91.9H), in Western blot and flowcytometric analyses, also decreased. In addition, the levels of MUC2 and MUC5B mucin gene expression measured by RT-PCR were reduced after DMSO-treatment, whereas the levels of MUC1, MUC5AC, and MUC6 mucin gene expression were not. The DMSO-treated cells were tested in vitro and in vivo for their properties. Differences were not detected in their anchorage-independent growth, anchorage-dependent growth, E-selectin-dependent cell adhesion or sensitivity to interleukin (IL)-2-activated lymphocyte cytolysis. When untreated or DMSO-treated LS174T cells were injected intrasplenically into nude mice, the treated cells lacking certain cell surface sulfomucins formed fewer metastatic colonies in the liver. These results suggest that the loss of sulfomucins by colonic epithelial cells during progression is not directly related to the enhanced malignant behavior.
Clin Exp Metastasis 1999 Mar
PMID:Malignant and other properties of human colon carcinoma cells after suppression of sulfomucin production in vitro. 1041 Nov

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.
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PMID:Expression of MUC5AC in colorectal carcinoma and relationship with prognosis. 1216 6

Intraductal papillary-mucinous tumours (IPMTs) of the pancreas are heterogeneous proliferations characterized by a malignant potential. The molecular mechanisms underlying the tumourigenesis process are not well understood. Recently, it has been shown that IPMTs secreting the mucin antigen MUC2 have a better prognosis, but the complete pattern of MUC gene expression has not yet been established. The aims of this study were to evaluate the mucin gene expression in 57 IPMTs and eight related lesions surgically resected and to relate MUC gene expression to the histological diagnosis. In situ hybridization (ISH) was performed in 28 cases with probes specific for the MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6, and MUC7 genes. An immunohistochemical analysis was carried in all 65 cases and in 90 conventional ductal adenocarcinomas of the pancreas using MUC1, MUC2, and MUC5AC antibodies. IPMTs of adenoma (dysplasia) type exhibited high expression of MUC2 (93%), MUC5AC (97%), and, to a lesser extent, of MUC4 (71%), all of which were also observed in colloid carcinomas associated with IPMTs. In contrast, IPMTs with simple hyperplasia, intraductal oncocytic papillary neoplasms, and pyloric glandular adenomas exhibited little or no expression of MUC2. The mucin expression profile supports the existence of two types of invasive tumour associated with IPMTs: a colloid and an ordinary form. The latter shows a pattern similar to the conventional ductal adenocarcinomas with a loss of MUC2 and a gain of MUC1 and has a greater tendency to metastasize. In conclusion, the altered expression of mucin, characteristic of IPMT of adenoma type and of colloid carcinomas, may contribute to the better clinical outcome of these neoplasms, compared to conventional pancreatic ductal adenocarcinomas.
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PMID:Mucin gene expression in intraductal papillary-mucinous pancreatic tumours and related lesions. 1221 83

Mucins are high-molecular weight epithelial glycoproteins with a high content of clustered oligosaccharides O-glycosidically linked to tandem repeat peptides rich in threonine, serine, and proline. There are two structurally and functionally distinct classes of mucins: secreted gel-forming mucins (MUC2, MUC5AC, MUC5B, and MUC6) and transmembrane mucins (MUC1, MUC3A, MUC3B, MUC4, MUC12, MUC17), although the products of some MUC genes do not fit well into either class (MUC7, MUC8, MUC9, MUC13, MUC15, MUC16). MUC1 mucin, as detected immunologically, is increased in expression in colon cancers, which correlates with a worse prognosis. Expression of MUC2 secreted gel-forming mucin is generally decreased in colorectal adenocarcinoma, but preserved in mucinous carcinomas, a distinct subtype of colon cancer associated with microsatellite instability. Another secreted gel-forming mucin, MUC5AC, a product of normal gastric mucosa, is absent from normal colon, but frequently present in colorectal adenomas and colon cancers. The O-glycosidically linked oligosaccharides of mucins can be described in terms of core type, backbone type, and peripheral structures. Colon cancer mucins have differences in both core carbohydrates and in peripheral carbohydrate structures that are being investigated as diagnostic and prognostic markers, and also as targets for cancer vaccines. Colon cancer mucins typically have increases in three core structures: Tn antigen (GalNAcalphaThr/Ser), TF antigen (Galbeta3GalNAc) and sialyl Tn (NeuAcalpha6GalNAc). The type 3 core (GlcNAcbeta3Ga1NAc) predominant in normal colonic mucin is lacking in colon cancer mucins. There are cancer-associated alterations in the peripheral carbohydrates of colonic mucins including a decrease in O-acetyl-sialic acid and a decrease in sulfation. There are, however, cancer-associated increases in sialyl LeX and related structures on mucins and other glycoproteins that can serve as ligands for selectins, increasing the metastatic capacity of colon cancer cells. The endogenous galactoside-binding protein galectin-3, which is expressed at higher levels in colon cancers than normal colon, binds to colon cancer mucin as well as other glycoproteins. Interference of the binding of selectins and galectin-3 to mucin may show therapeutic or preventative promise for colon cancer.
Cancer Metastasis Rev
PMID:Mucins and mucin binding proteins in colorectal cancer. 1500 Jan 51

Molecular changes are vital for the development of prognostic markers and therapeutic modalities of prostate cancer (CaP). There is growing interest in mucins as treatment targets in human malignancies, including CaP. The role of their expression in the progression of CaP is however unclear. We examined the expressions MUC1, MUC2, MUC4, MUC5AC and MUC6 in CaP tissues using tissue microarrays (TMAs) to look for tumor-associated antigens (TAAs) for targeted therapy. In this study, 120 paraffin-embedded specimens were selected from patients who underwent radical retro-pubic prostatectomy (RRP) or trans-urethral-resection of the prostate (TURP) for primary, untreated CaP and 10 matched lymph node metastases. A series of MUC monoclonal antibodies (mAbs) was used on TMAs by standard immunohistochemistry. Our results indicate that the over-expression of MUC1 was detected in 58% of primary CaP tissues and 90% of lymph node metastases but not in normal prostate or benign tissues, while the expression of MUC2, MUC4, MUC5AC and MUC6 was found to be negative in both normal and cancer tissues. Of the MUC1 positive tumors 86% were Gleason grade 7 or higher. Over-expression of MUC1 was found in late stage CaP while MUC2, 4, 5AC and 6 were negative in CaP. MUC1 is a TAA that is highly related to tumor progression in CaP patients. This antigen is ideal for targeted therapy to control micrometastases and hormone refractory disease but additional studies are necessary to assess its usefulness in patient biopsies and CaP bone metastases before clinical trial.
Clin Exp Metastasis 2005
PMID:MUC1, MUC2, MUC4, MUC5AC and MUC6 expression in the progression of prostate cancer. 1647 27

Lewis antigens are terminal fucosylated oligosaccharides synthesized by the sequential action of several glycosyltransferases. The fucosyltransferases are the enzymes responsible for the addition of terminal fucose to precursor oligosaccharides attached to proteins or lipids. These oligosaccharides, defined as cell surface markers, have been implicated in different types of intercellular interactions and in adhesion and invasion processes. Transfection of HT-29/M3 colon cancer cells with the full length of human fucosyltransferase (FUT1), induces the synthesis of H type 2 and Lewis y antigens, associated with a decrease of sialyl-Lewis x. The capacity to develop primary tumors when cells were injected intrasplenically was similar in parental and FUT1-transfected cells, but the capacity to colonize the liver after spleen removal was significantly reduced in M3/FUT1 transfected cells. These results indicate that the expression of FUT1 induces changes in the metastatic capacity of HT-29/M3 colon cancer cells, as a consequence of the altered expression pattern of type 2 Lewis antigens. Also, an association between MUC5AC expression and the degree of gland differentiation in both primary splenic tumors and hepatic metastases was detected.
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PMID:Changes in the invasive and metastatic capacities of HT-29/M3 cells induced by the expression of fucosyltransferase 1. 1745 61

Pseudomyxoma peritonei (PMP) is a clinical condition initially thought to be related to ovarian mucinous tumors; however, immunohistochemistry and molecular biology techniques have convincingly made the link to appendiceal mucinous neoplasms, resulting in changes in histologic and clinical approaches. The objective of this study was to compare the immunohistochemical profile of ovarian tumors associated with PMP and intestinal mucinous ovarian neoplasms without PMP. The study was retrospective and included 28 intestinal ovarian mucinous tumors selected from the files of the Division of Surgical Pathology of the University of Sao Paulo Medical School, from 1996 to 2005. Seven cases were associated with PMP of disseminated peritoneal adenomucinosis-type and all presented borderline histology. Immunohistochemical staining for mucin genes products (MUC1, MUC2, MUC5AC, and MUC6), CK7, CK20, CA19.9, and CA125 were performed in tissue microarrays. Of note, we detected differences in the expression of MUC2 and CK20 between cases with and without PMP. Comparisons of borderline histology with that of benign/malignant tumors also revealed differences in MUC2 and CK20. Our results confirm that there is a distinct profile of intestinal ovarian tumors associated with pseudomyxoma, particularly with respect to the expression of the gel-forming mucin MUC2. The profile of borderline tumors, even in cases without PMP, was distinct from that of other primary mucinous tumors of the intestinal type, suggesting that borderline histology may represent a secondary tumor or a less aggressive variant of PMP. An appendiceal origin seems the most probable for this group of neoplasias.
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PMID:Mucinous ovarian tumors associated with pseudomyxoma peritonei of adenomucinosis type: immunohistochemical evidence that they are secondary tumors. 1751 4

Prognostic factors for ampullary carcinomas (ACs) are poorly defined. Fifty three resected ACs were analyzed for CDX2, MUC1, MUC5AC, MUC6, MUC2, and for mismatch repair proteins (hMLH1, hMSH2, PMS2, hMSH6) using immunohistochemistry. Microsatellite instability (MSI) status was evaluated by fluorescently labeled PCR using an automated sequencer. Univariate and multivariate analysis was performed for clinicopathological, immunohistochemical and molecular parameters. CDX2 was found in 32 out of 53 (60%) ACs with a significantly higher frequency among intestinal ACs compared with biliopancreatic (BP) ACs. The MUC1, MUC5AC, MUC6, MUC2 apomucins were expressed in 75, 43, 39, and 28% of ACs, respectively, with a significantly higher coexpression of MUC1/MUC5AC in BP ACs. MSI and loss of expression of hMLH1/PMS2 or hMSH2/hMSH6 proteins were observed only in intestinal ACs. Factors significantly correlated with improved survival in the univariate analysis were: low stage, absence of lymph nodes metastases, negative surgical margins (R0 status), and presence of MSI. In the multivariate analysis, stage was the only independent prognostic factor of survival. We conclude that stage is the only independent prognostic factor of survival in the multivariate analysis, whereas histological criteria and the immunohistochemical expression of apomucins and CDX2 are helpful in the classification and understanding of the histogenesis of ACs.
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PMID:Prognostic factors for ampullary adenocarcinomas: tumor stage, tumor histology, tumor location, immunohistochemistry and microsatellite instability. 1765 61

A case of a colonic carcinoma showing a pancreatic acinar cell differentiation is described for the first time. A 65-year-old woman underwent surgical resection for an ulcerated protruding tumour of 4 x 2.5 cm in size on the anterior wall of the sigmoid colon. Histologically, tumour cells were organized in acinar structures resembling pancreatic acini and in solid nests and ribbons or diffusely infiltrated as poorly cohesive cells. Lymph nodes and femur metastases displayed the same histological features. The ultrastructural analysis of the primary tumour indicated the presence of zymogen-like granules in the cytoplasm of tumour cells. Immunohistochemically, both acinar and diffuse patterns of growth showed an intense staining for trypsin, chymotrypsin and BCL10 and a weaker immunoreactivity for lipase and carboxyl ester hydrolase. Most tumour cells were cytokeratin 20, CDX2 and p53 positive; whereas, mucin (MUC)2 immunoreactivity was observed only in the signet ring cells present in the diffuse pattern and chromogranin A in rare isolated tumour cells. No immunoreactivity was observed for cytokeratin 7, MUC1, MUC5AC, pancreatic amylase or PDX1. There was no evidence of a pancreatic acinar cell carcinoma or of heterotopic pancreatic tissue. A colonic origin ought to be suspected when a metastatic carcinoma of unknown primary shows an acinar differentiation.
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PMID:Colonic carcinoma with a pancreatic acinar cell differentiation. A case report. 1990 63


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