Differential apomucin expression in normal and neoplastic human gastrointestinal tissues

Carrato, Cristina; Balagué, Cristina; Bolós, Carme de; González, Eduardo; Gambús, Gemma; Planas, Josep V.; Périni, Jean-Marc; Andreu, David; Real, Francisco X.

doi:10.1016/0016-5085(94)90073-6

Cited by 145 publications

(107 citation statements)

References 40 publications

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“…19,47 MUC5B and MUC6 expression in the lower gastrointestinal tract has remained relatively unexplored. MUC5B has been detected in normal colon where expression appears to be restricted to goblet cells, 15,48 and in the only study to date, MUC5B expression in 3/8 colorectal cancers was diffusely and strongly positive. 44 Similarly, MUC6 expression in colorectal tumors has been restricted largely to adenomas and serrated polyps, the latter have been found to express MUC6 commonly, 30,49 whereas several groups have reported MUC6 expression in cancers as rare or absent, 16,50,51 even in mucinous carcinomas.…”

Section: Discussionmentioning

confidence: 93%

Expression of MUC2, MUC5AC, MUC5B, and MUC6 mucins in colorectal cancers and their association with the CpG island methylator phenotype

et al. 2013

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Mucinous differentiation is associated with both CpG island methylator phenotype and microsatellite instability in colorectal cancer. The mucinous phenotype derives from abundant expression of the colonic goblet cell mucin, MUC2, and de novo expression of gastric foveolar mucin, MUC5AC. We, therefore, investigated the protein expression levels of MUC2 and MUC5AC, as well as MUC5B and MUC6, in molecular subtypes of colorectal cancer. Seven-hundred and twenty-two incident colorectal carcinomas occurring in 702 participants of the Melbourne Collaborative Cohort Study were characterized for methylator status, MLH1 methylation, somatic BRAF and KRAS mutations, microsatellite-instability status, MLH1, MSH2, MSH6, and PMS2 mismatch repair, and p53 protein expression, and their histopathology was reviewed. Protein expression levels of MUC2, MUC5AC, MUC5B, MUC6, and the putative mucin regulator CDX2 were compared with molecular and clinicopathological features of colorectal cancers using odds ratios and corresponding 95% confidence intervals. MUC2 overexpression (425% positive tumor cells) was observed in 33% colorectal cancers, MUC5B expression in 53%, and de novo MUC5AC and MUC6 expression in 50% and 39%, respectively. Co-expression of two or more of the mucins was commonly observed. Expression of MUC2, MUC5AC and MUC6 was strongly associated with features associated with tumorigenesis via the serrated neoplasia pathway, including methylator positivity, somatic BRAF p.V600E mutation, and mismatch repair deficiency, as well as proximal location, poor differentiation, lymphocytic response, and increased T stage (all Po0.001). Overexpression was observed in tumors with and without mucinous differentiation. There were inverse associations between expression of all four mucins and p53 overexpression. CDX2 expression was inversely associated with MUC2, MUC5AC and MUC6 expression. Our results suggest that, in methylator-positive tumors, mucin genes on chromosome 11p15.5 region undergo increased expression via mechanisms other than direct regulation by CDX2.

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Section: Discussionmentioning

confidence: 93%

Expression of MUC2, MUC5AC, MUC5B, and MUC6 mucins in colorectal cancers and their association with the CpG island methylator phenotype

et al. 2013

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“…Gastric cancers have been found to contain higher levels of MUC1 mucin expression than normal gastric mucosa, and the expression of MUC2 mucin was observed frequently in intestinal type gastric cancer (37,38). As MSIϩ gastric cancers were significantly associated with intestinal subtype, it is expected that MSIϩ gastric cancers showed higher expression of MUC2 mucin than MSIϪ cancers.…”

Section: Discussionmentioning

confidence: 99%

Distinct Clinical Features and Outcomes of Gastric Cancers with Microsatellite Instability

et al. 2002

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Microsatellite instability (MSI) is a hallmark of theAlthough the incidence rate of gastric cancer has been declining steadily, gastric cancer remains the second most common malignant tumor in the world (1, 2) and contributes to significant cancer mortality, particularly in Asia (China, Japan, and Korea) and parts of Europe and Latin America. Multiple environmental factors, including Helicobacter pylori infection (3) and dietary factors (4), have been implicated in the initiation of gastric carcinogenesis. Although much has been learned recently about the molecular genetic alterations associated with the development of gastric cancers, much about them still has remained unclear. Microsatellite instability (MSI) is a form of genomic instability associated with defective DNA mismatch repair in tumors (5). The majority of cancers of the hereditary nonpolyposis colon cancer (HNPCC) syndrome (6) and about 15% of unselected colorectal cancers have MSIϩ phenotype (7). Clinicopathologic characteristics of MSIϩ colorectal cancers are proximal location, younger age, lower lymph node metastasis, and a better survival rate (7,8). The stomach is a frequent site of extracolonic cancer development in patients with HNPCC (9) and is one of the organs in which primary sporadic tumors show MSIϩ phenotype (10 -15). Defects of the mismatch repair system and MSI play an important role in early stage of gastric carcinogenesis. In the adenoma-carcinoma sequence of the stomach, gastric adenoma had a high frequency of MSI, and it persisted after malignant transformation (16). To determine the correlations between MSI status and clinicopathologic variables

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“…In earlier studies, almost all of the known human mucin genes have been shown to be expressed at some level in the human gall bladder epithelium [29,47,49,50]. Since these studies have been conducted in numerous laboratories using different techniques and have examined both normal and inflamed gall bladder tissue, it is difficult to conclude which of these genes encodes the predominant gall bladder mucin.…”

Section: Discussionmentioning

confidence: 99%

Molecular cloning of a major human gall bladder mucin: complete C-terminal sequence and genomic organization of MUC5B

Keates

Nunes

Afdhal

et al. 1997

Biochemical Journal

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Gall bladder mucin has been shown to play a central role in the pathogenesis of cholesterol gallstone disease. While cloning and sequencing studies have provided a wealth of information on the structure of other gastrointestinal and respiratory mucins, nothing is known about the primary structure of human gall bladder mucin. In this study, we show that the tracheobronchial mucin MUC5B is a major mucin gene product expressed in the gall bladder. Antibodies directed against deglycosylated human gall bladder mucin were used to screen a gall bladder cDNA expression library, and most of the isolated clones contained repetitive sequences nearly identical with those in the tandem repeat region of MUC5B. An additional clone (hGBM2-3) contained an open reading frame coding for a 389 residue cysteine-rich sequence. The arrangement of cysteine residues in this sequence was very similar to that in the C-terminal regions of MUC2, MUC5AC and human von Willebrand factor. This cysteine-rich sequence was connected to a series of degenerate MUC5B tandem repeats in a 7.5 kb HincII genomic DNA fragment. This fragment, with ten exons and nine introns, contained MUC5B repeats in exon 1 and a 469 residue cysteine-rich sequence in exons 2–10 that provided a 152 nucleotide overlap with cDNA clone hGBM2-3. Interestingly, the exon–intron junctions in the MUC5B genomic fragment occurred at positions equivalent to those in the D4 domain of human von Willebrand factor, suggesting that these proteins evolved from a common evolutionary ancestor through addition or deletion of exons encoding functional domains.

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Differential apomucin expression in normal and neoplastic human gastrointestinal tissues

Cited by 145 publications

References 40 publications

Expression of MUC2, MUC5AC, MUC5B, and MUC6 mucins in colorectal cancers and their association with the CpG island methylator phenotype

Expression of MUC2, MUC5AC, MUC5B, and MUC6 mucins in colorectal cancers and their association with the CpG island methylator phenotype

Distinct Clinical Features and Outcomes of Gastric Cancers with Microsatellite Instability

Molecular cloning of a major human gall bladder mucin: complete C-terminal sequence and genomic organization of MUC5B

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