Comparison between colorectal low- and high-grade mucinous adenocarcinoma with MUC1 and MUC5AC

Onodera, Masayuki; Nishigami, Takashi; Torii, Ikuko; Sato, Ayuko; Tao, Lihua; Kataoka, Tatsuki R.; Yoshikawa, Reigetsu; Tsujimura, Tohru

doi:10.4251/wjgo.v1.i1.69

Cited by 5 publications

(4 citation statements)

References 17 publications

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“…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. 52 In 1999, Toyota et al 53 described the existence of the CIMP in colorectal carcinoma, in which hypermethylation is induced in a wide variety of genes. Ferracin et al 9 found that CIMP-positive colorectal cancers were more likely than CIMPnegative cancers to show areas of mucinous differentiation.…”

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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“…Mucinous components were divided into two groups by the quality of mucin (low or high grade) (20). The Q score for mucinous components was calculated by multiplying the quality of mucin by the proportion of the area.…”

Section: Kras Mutation Analysismentioning

confidence: 99%

Histology and its prognostic effect on KRAS‑mutated colorectal carcinomas in Korea

2020

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KRAS mutation is frequently identified in advanced colorectal carcinoma (CRC); however, its prognostic significance and the associated histological features have remained to be clarified. In the present study, the precise histological results and prognostic value of KRAS-mutated CRCs were investigated in patients from South Korea. A retrospective review of the results from KRAS mutation testing, as well as evaluation of the histology of 310 cases of CRC at various stages, were performed. Cross-tabulation and survival analysis were performed according to the KRAS status. Patients with KRAS mutation more frequently exhibited serrated and papillary architectures (P= 0.009 and P= 0.014, respectively). KRAS mutation was an independent unfavorable prognostic factor for overall survival (OS) according to multivariate analysis (P= 0.001), whereas no association was observed with disease-free survival (DFS) (P= 0.611). Of note, in the subgroup of KRAS-mutated carcinomas, the presence of a solid component on histology was associated with less favorable OS (P= 0.032). Furthermore, among the wild type cases, patients with a micropapillary component had a worse OS than those who did not (P=0.018). However, no subgroup or specific histological features were associated with DFS. In summary, KRAS-mutated CRCs had a moderate association with particular histological features, and according to the KRAS mutational status, there was a certain degree of association between histology and prognosis.

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“…Studies have shown that during adenoma-adenocarcinoma progression, the expression of MUC5AC is upregulated[ 41 ], which may be associated with transcription factors such as Smad-4, SP-1[ 45 ], GATA-6 and HNF-4α[ 46 ], sex determining region Y-box 2[ 47 ], and trefoil factor 3[ 48 ]. Although MUC5AC expression is upregulated in MAC, the expression of MUC5AC in low-grade MAC is significantly higher than that of high-grade MAC[ 4 ]. At the same time, the lack of MUC5AC expression is an indication of more aggressive colorectal tumors, as patients with negative MUC5AC expression have a poorer prognosis than those with positive expression[ 49 ].…”

Section: Molecular Characteristics Of Colorectal Macmentioning

confidence: 99%

“…Compared to non-MAC (NMAC), the clinicopathological characteristics, molecular features, response to chemo-/radiotherapy, and prognosis of MAC are evidently different. MAC are divided into two types based on the degree of histological structural differences: One type is the low-grade MAC, which originates from well-differentiated to moderately differentiated adenocarcinoma and papillary carcinoma, whereas the other type is the high-grade MAC, originated from poorly differentiated adenocarcinoma and signet ring cell carcinoma (SRCC)[ 4 ]. Currently, the prognosis of MAC remains controversial.…”

Section: Introductionmentioning

confidence: 99%

Mucinous adenocarcinoma: A unique clinicopathological subtype in colorectal cancer

Huang¹,

Yang²,

Shi³

et al. 2021

WJGS

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Mucinous adenocarcinoma (MAC) is a unique clinicopathological subtype of colorectal cancer, which is characterized by extracellular mucinous components that comprise at least 50% of the tumor tissue. The clinical characteristics, molecular features, response to chemo-/radiotherapy, and prognosis of MAC are different from that of non-MAC (NMAC). MAC is more common in the proximal colon, with larger volume, higher T-stage, a higher proportion of positive lymph nodes, poorer tumor differentiation, and a higher proportion of peritoneal implants compared to NMAC. Although biopsy is the main diagnostic method for MAC, magnetic resonance imaging is superior in accuracy, especially for rectal carcinoma. The aberrant expression of mucins, including MUC1, MUC2 and MUC5AC, is a notable feature of MAC, which may be related to tumor invasion, metastasis, inhibition of apoptosis, and chemo-/radiotherapy resistance. The genetic origin of MAC is mainly related to BRAF mutation, microsatellite instability, and the CpG island methylator phenotype pathway. In addition, the poor prognosis of rectal MAC has been confirmed by various studies, and that of colonic MAC is still controversial. In this review, we summarize the epidemiology, clinicopathological characteristics, molecular features, methods of diagnosis, and treatments of MAC in order to provide references for further fundamental and clinical research.

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Comparison between colorectal low- and high-grade mucinous adenocarcinoma with MUC1 and MUC5AC

Abstract: AIM:To explore useful prognostic factors for mucinous adenocarcinoma (MAC) in the colon and rectum.

Cited by 5 publications

References 17 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

Histology and its prognostic effect on KRAS‑mutated colorectal carcinomas in Korea

Mucinous adenocarcinoma: A unique clinicopathological subtype in colorectal cancer

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