MUC1, MUC2, MUC5AC, and MUC6 in colorectal cancer: expression profiles and clinical significance

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Abstract

Mucin glycoprotein expression can be altered during the carcinogenic process. The impact on the prognosis of patients with colorectal cancer (CRC) is controversial. We analyzed tumors from 381 patients for MUC1, MUC2, MUC5AC, and MUC6 expression by immunohistochemical staining, using tissue microarrays. Progression-free and cancer-specific survival were determined using the Kaplan-Meier method. Expression of intestinal mucin MUC2 was lost in 85 (23 %) CRCs, and patients with MUC6-negative tumors showed shorter progression-free survival (PFS, p = 0.043). Gastric mucins MUC5AC and MUC6 showed high (>50 %) aberrant expression in 28 (8 %) and 9 (2 %) cases, respectively. High expression of MUC5AC was associated with longer PFS ( p = 0.055). High expression of MUC6 was associated with 100 % PFS ( p = 0.024) and longer cancer-specific survival (CSS, p = 0.043). MUC1 was expressed in 238 (64 %) tumors and had no impact on outcome. When analysis was restricted to stages II and III, loss of MUC2 was associated with adverse outcome. Overexpression of both MUC5AC and MUC6 significantly predicted favorable PFS and CSS. In conclusion, loss of MUC2 expression proved to be a predictor of adverse outcome, while the gain of aberrant expression of MUC5AC and particularly of MUC6 was associated with favorable outcome in CRC, notably in intermediate stages II and III.

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Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma.

C MOERTEL, T Fleming, J S Macdonald … (1990)

Twelve hundred ninety-six patients with resected colon cancer that either was locally invasive (Stage B2) or had regional nodal involvement (Stage C) were randomly assigned to observation or to treatment for one year with levamisole combined with fluorouracil. Patients with Stage C disease could also be randomly assigned to treatment with levamisole alone. The median follow-up time at this writing is 3 years (range, 2 to 5 1/2). Among the patients with Stage C disease, therapy with levamisole plus fluorouracil reduced the risk of cancer recurrence by 41 percent (P less than 0.0001). The overall death rate was reduced by 33 percent (P approximately 0.006). Treatment with levamisole alone had no detectable effect. The results in the patients with Stage B2 disease were equivocal and too preliminary to allow firm conclusions. Toxic effects of levamisole alone were infrequent, usually consisting of mild nausea with occasional dermatitis or leukopenia, and those of levamisole plus fluorouracil were essentially the same as those of fluorouracil alone--i.e., nausea, vomiting, stomatitis, diarrhea, dermatitis, and leukopenia. These reactions were usually not severe and did not greatly impede patients' compliance with their regimen. We conclude that adjuvant therapy with levamisole and fluorouracil should be standard treatment for Stage C colon carcinoma. Since most patients in our study were treated by community oncologists, this approach should be readily adaptable to conventional medical practice.

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Mucins and mucin binding proteins in colorectal cancer.

James Byrd, Robert Bresalier (2015)

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.

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A new prognostic classification of rectal cancer.

J Northover, J Jass, S Love (1987)

Only 60% of patients having radical surgery for rectal cancer are cured of their disease. The ideal system of classification would identify just two categories--the cured and those who will die of their disease. Specimens from 379 patients who had undergone radical surgery for rectal cancer more than 20 years ago were re-examined in order to identify discrete pathological variables that independently influence long-term survival. The selected variables were given weighted scores and the score range was divided to provide four prognostic groups. The model was tested on a second data set comprising 331 patients and gave similar results. The new prognostic classification is simple to use and is superior to staging by the method of Dukes because it places twice as many patients into groups that provide a confident prediction of clinical outcome.

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Author and article information

Contributors

Cord Langner: +43 316 385 13665 , +43 316 385 13432 , cord.langner@medunigraz.at

Journal

Journal ID (nlm-ta): Virchows Arch

Journal ID (iso-abbrev): Virchows Arch

Title: Virchows Archiv

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0945-6317

ISSN (Electronic): 1432-2307

Publication date (Electronic): 14 June 2016

Publication date PMC-release: 14 June 2016

Publication date (Print): 2016

Volume: 469

Issue: 3

Pages: 255-265

Affiliations

[1 ]Department of Medicine II, University Hospital Mannheim, Medical Faculty Mannheim: Heidelberg University, Mannheim, Germany

[2 ]Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria

[3 ]Department of Medicine II, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

[4 ]Department of Surgery, Medical University of Innsbruck, Innsbruck, Austria

[5 ]Department of Surgery, Division of General Surgery, Medical University of Graz, Graz, Austria

Article

Publisher ID: 1970

DOI: 10.1007/s00428-016-1970-5

PMC ID: 5007278

PubMed ID: 27298226

SO-VID: 84350d8e-034b-4714-8647-181b5234bba7

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Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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ScienceOpen disciplines: Pathology

Keywords: mucin,prognosis,stage ii,immunohistochemistry,large intestine,prognostic factor

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ScienceOpen disciplines: Pathology

Keywords: mucin, prognosis, stage ii, immunohistochemistry, large intestine, prognostic factor

MUC1, MUC2, MUC5AC, and MUC6 in colorectal cancer: expression profiles and clinical significance

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Most cited references 32

Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma.

Mucins and mucin binding proteins in colorectal cancer.

A new prognostic classification of rectal cancer.

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