Comparative evaluation of the prognostic value of MUC1, MUC2, sialyl‐Lewis<sup>a</sup> and sialyl‐Lewis<sup>x</sup> antigens in colorectal adenocarcinoma

Se, Baldus; Mönig, SP; Fg, Hanisch; Tk, Zirbes; Flucke, Uta; Oelert, S; G, Zilkens; Madejczik, B; Thiele, Jürgen; Pm, Schneider; Hölscher, AH; Dienes, HP

doi:10.1046/j.1365-2559.2002.01389.x

Cited by 94 publications

(84 citation statements)

References 35 publications

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“…19,20,40 Various immunohistochemical studies have reported MUC2 positivity in colorectal cancers ranging from 21 to 63%. 19,39,[41][42][43] MUC5AC expression has been reported in 13-64% carcinomas, 16,42,44,45 with highest levels of expression in microsatellite-unstable/mismatch repair-deficient tumors 18,19,46 and those showing characteristic mucinous phenotype. 19,47 MUC5B and MUC6 expression in the lower gastrointestinal tract has remained relatively unexplored.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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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“…Prognostic evaluations point to a functional impact of both determinants, and an increased expression of sialyl Lewis x correlated with the extent of malignancy and the high incidence of recurrence (and consequently with survival) of colon carcinoma patients (Nakamori et al, 1993). However, recent studies disagree with this conclusion, pinpointing a correlation of sialyl Lewis x (but not the Lewis a isomer) expression with progression of lymph node metastasis and dedifferentiation but not its status as an independent prognostic factor in colorectal adenocarcinomas (Baldus et al, 2002;Matsumoto et al, 2002). An important point to be noted for comparison is the nature of the mAb used as fine-specificity differences are encountered between various preparations (Matsumoto et al, 2002).…”

Section: Hittelet Et Almentioning

confidence: 98%

Binding Sites for Lewis Antigens Are Expressed by Human Colon Cancer Cells and Negatively Affect Their Migration

Hittelet

Camby

Nagy

et al. 2003

Laboratory Investigation

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SUMMARY:In colon cancer, endothelial cell selectins can promote tumor cell attachment via interactions with sialylated Lewis antigens present at the surface of tumor cells, thereby facilitating tumor cell arrest and transmigration into the extravascular space. However, it is not known whether Lewis antigens interact with colon tumor cells and modify their migration. Our aim was to detect the presence of binding sites on human tumor cells for Lewis a/x antigens and their sialylated derivatives in vitro and in vivo and to analyze their influence on migration of colon cancer cells. The immunocytochemical and histochemical levels of expression of the four Lewis antigens were quantitatively determined in four human colon cancer cell lines and in in vivo nude mice xenografts. The levels of expression of specific binding sites for these sugar epitopes were determined by synthetic neoglycoconjugates. The influence of binding of these carbohydrate ligands on cancer cell migration was quantitatively evaluated by computer-assisted phase-contrast videomicroscopy performed on Matrigel culture supports either left uncoated or coated with neoglycoconjugate presenting synthetic Lewis a , sialyl Lewis a , Lewis x , or sialyl Lewis x antigens. The influence of the calcium concentration in the culture medium on the Lewis antigen-mediated effects was checked. Human colon cancer cells expressed significant amounts of specific binding sites detected by the synthetic probes in addition to the oligosaccharide epitopes. The expression levels differed considerably between the four cell lines and between in vitro and in vivo specimens. Cell migration analysis revealed that the four Lewis antigens markedly decreased the levels of migration of the HCT-15 and LoVo cancer cells. This effect depends on the calcium concentration in the culture medium. Binding sites for Lewis epitopes are present on colon cancer cells. The functional relevance of these sites is indicated by the negative influence on cell migration of a matrix containing the oligosaccharides as ligand parts. (Lab Invest 2003, 83:777-787).

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“…Unlike normal epithelium, MUC1 is found throughout the tumor mass and is broadly expressed on the tumor surface in the underglycosylated form [10]. Increased expression of underglycosylated MUC1 has been documented in adenomatous polyps as well as colorectal adenocarcinomas [11][12][13]. Underglycosylation of MUC1 leads to exposure of cryptic epitopes that can be recognized by cytotoxic T lymphocytes (CTL) [14,15].…”

Section: Introductionmentioning

confidence: 99%

Characterization of the MUC1.Tg/MIN transgenic mouse as a model for studying antigen-specific immunotherapy of adenomas

Akporiaye

Bradley-Dunlop

Gendler

et al. 2007

Vaccine

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A bigenic MUC1.Tg/MIN mouse model was developed by crossing Apc/ MIN/+ (MIN) mice with human MUC1 transgenic mice to evaluate MUC1 antigen-specific immunotherapy of intestinal adenomas. The MUC1.Tg/MIN mice developed adenomas at a rate comparable to that of MIN mice and had similar levels of serum MUC1 antigen. A MUC1-based vaccine consisting of MHC class I-restricted MUC1 peptides, a MHC class II-restricted pan-helper peptide, unmethylated CpG oligodeoxynucleotide and GM-CSF caused flattening of adenomas and significantly reduced the number of large adenomas. Immunization was successful in generating a MUC1-directed immune response evidenced by increased MUC1 peptide-specific anti-tumor cytotoxicity and IFN-γ secretion by lymphocytes.

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Comparative evaluation of the prognostic value of MUC1, MUC2, sialyl‐Lewis^a and sialyl‐Lewis^x antigens in colorectal adenocarcinoma

Abstract: 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.

Cited by 94 publications

References 35 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

Binding Sites for Lewis Antigens Are Expressed by Human Colon Cancer Cells and Negatively Affect Their Migration

Characterization of the MUC1.Tg/MIN transgenic mouse as a model for studying antigen-specific immunotherapy of adenomas

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Comparative evaluation of the prognostic value of MUC1, MUC2, sialyl‐Lewisa and sialyl‐Lewisx antigens in colorectal adenocarcinoma

Abstract: 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.

Cited by 94 publications

References 35 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

Binding Sites for Lewis Antigens Are Expressed by Human Colon Cancer Cells and Negatively Affect Their Migration

Characterization of the MUC1.Tg/MIN transgenic mouse as a model for studying antigen-specific immunotherapy of adenomas

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Comparative evaluation of the prognostic value of MUC1, MUC2, sialyl‐Lewis^a and sialyl‐Lewis^x antigens in colorectal adenocarcinoma