Altered expression of MUC2 and MUC5AC in progression of colorectal carcinoma

Bu, Xiaodong; Li, Nan; Tian, Xiaoqiang; Li, Li; Wang, Jinsong; Yu, Xiaofang; Huang, Peilin

doi:10.3748/wjg.v16.i32.4089

Cited by 48 publications

(63 citation statements)

References 29 publications

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“…The older patients with carcinoma showed MUC-5AC overexpression, in comparison to the young (p<0.05). MUC-5AC expression was negatively associated with the depth of invasion, venous invasion, gastric NNM than gastric cancer in agreement with the data in ovarian carcinogenesis (Feng et al, 2002), indicating that down-regulated MUC-2 might play an important role in gastric carcinogenesis in agreement with another study (Bu et al, 2010). Additionally, MUC-2 expression was negatively correlated with tumor size, depth of invasion, and TNM staging of gastric cancer, in line with the previous reports (Rakha et al, 2005;İlhan et al, 2010), suggesting that reduced MUC-2 expression might be closely linked to the growth, invasion and progression of gastric cancer.…”

Section: Discussionsupporting

confidence: 81%

Clinicopathological and Prognostic Significance of MUC-2, MUC-4 and MUC-5AC Expression in Japanese Gastric Carcinomas

Xiao¹,

Zhao²,

Zhao³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Section: Discussionsupporting

confidence: 81%

Clinicopathological and Prognostic Significance of MUC-2, MUC-4 and MUC-5AC Expression in Japanese Gastric Carcinomas

Xiao¹,

Zhao²,

Zhao³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…Similar observations regarding BRAF V600E in signet ring cell carcinoma have been noted by Ogino et al 35 Expression of the gastric mucin MUC5AC, a typical feature of serrated polyps, is also more common in mucinous and signet ring cell carcinomas, but is relatively uncommon in conventional adenocarcinoma. [47][48][49] These findings suggest that a subset of signet ring cell carcinoma may be related to the serrated pathway of carcinogenesis.…”

Section: Discussionmentioning

confidence: 86%

Loss of heterozygosity, aberrant methylation, BRAF mutation and KRAS mutation in colorectal signet ring cell carcinoma

et al. 2012

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The relationship of molecular abnormalities with clinicopathologic features and survival in colorectal signet ring cell carcinoma, and its comparison with mucinous and conventional adenocarcinomas, has not been well studied. High-level microsatellite instability, loss of heterozygosity (LOH) at four loci, CpG island methylation phenotype based on seven loci, BRAF V600E mutation and KRAS mutation in signet ring cell carcinoma were compared with mucinous and conventional adenocarcinomas. The relationship of these molecular features in signet ring cell carcinoma with clinicopathologic features and survival was examined. LOH was observed in 93% of signet ring cell carcinomas compared with 62 and 70% of mucinous and conventional adenocarcinomas. Also, 80% of signet ring cell carcinomas with high-level microsatellite instability showed LOH compared with 14% each of mucinous and conventional adenocarcinomas. High-level microsatellite instability, CpG island methylation phenotype-positive status and BRAF V600E mutation were more often seen in signet ring cell carcinoma and mucinous adenocarcinoma compared with conventional adenocarcinoma. BRAF V600E mutation was significantly associated with CpG island methylation phenotype-positive status. Stage and BRAF V600E mutation in microsatellite-stable cases were the only variables with an affect on survival. In conclusion, chromosomal instability manifested by LOH is nearly a universal finding in signet ring cell carcinoma, including cases with highlevel microsatellite instability. This may explain the aggressive behavior of signet ring cell carcinoma irrespective of high-level microsatellite-instability status. BRAF V600E mutation and CpG island methylation phenotypepositive status are similar in signet ring cell carcinoma and mucinous adenocarcinoma but more frequent when compared with conventional adenocarcinoma. In signet ring cell carcinoma, BRAF V600E mutation adversely affects survival in microsatellite-stable tumors, but not in high-level microsatellite-unstable tumors. The high frequency of methylation and BRAF V600E mutation suggests that many signet ring cell carcinomas may be related to the serrated pathway of carcinogenesis.

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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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Altered expression of MUC2 and MUC5AC in progression of colorectal carcinoma

Abstract: Alterations in MUC expression occur during colorectal tumorigenesis. The transformation process in MC and SRCC may be different from that in the traditional adenoma-carcinoma sequence.

Cited by 48 publications

References 29 publications

Clinicopathological and Prognostic Significance of MUC-2, MUC-4 and MUC-5AC Expression in Japanese Gastric Carcinomas

Clinicopathological and Prognostic Significance of MUC-2, MUC-4 and MUC-5AC Expression in Japanese Gastric Carcinomas

Loss of heterozygosity, aberrant methylation, BRAF mutation and KRAS mutation in colorectal signet ring cell carcinoma

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

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