MUC1, MUC2, MUC5AC, and MUC6 in Colorectal Cancer: Expression Profiles and Clinical Significance

Overview

Journal Virchows Arch

Specialties Cell Biology
Molecular Biology
Pathology

Date 2016 Jun 15

PMID 27298226

Citations 71

Authors

Johannes Betge

Nora I Schneider

Lars Harbaum

Marion J Pollheimer

Richard A Lindtner

Peter Kornprat

Matthias P Ebert

Cord Langner

Affiliations

Soon will be listed here.

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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References

Byrd J, Bresalier R . Mucins and mucin binding proteins in colorectal cancer. Cancer Metastasis Rev. 2004; 23(1-2):77-99. DOI: 10.1023/a:1025815113599. View

Ueno H, Murphy J, Jass J, Mochizuki H, Talbot I . Tumour 'budding' as an index to estimate the potential of aggressiveness in rectal cancer. Histopathology. 2002; 40(2):127-32. DOI: 10.1046/j.1365-2559.2002.01324.x. View

Duncan T, Watson N, Al-Attar A, Scholefield J, Durrant L . The role of MUC1 and MUC3 in the biology and prognosis of colorectal cancer. World J Surg Oncol. 2007; 5:31. PMC: 1828734. DOI: 10.1186/1477-7819-5-31. View

Hiraga Y, Tanaka S, Haruma K, Yoshihara M, Sumii K, Kajiyama G . Immunoreactive MUC1 expression at the deepest invasive portion correlates with prognosis of colorectal cancer. Oncology. 1998; 55(4):307-19. DOI: 10.1159/000011868. View

Harbaum L, Pollheimer M, Kornprat P, Lindtner R, Schlemmer A, Rehak P . Keratin 7 expression in colorectal cancer--freak of nature or significant finding?. Histopathology. 2011; 59(2):225-34. DOI: 10.1111/j.1365-2559.2011.03694.x. View

Compton C . Optimal pathologic staging: defining stage II disease. Clin Cancer Res. 2007; 13(22 Pt 2):6862s-70s. DOI: 10.1158/1078-0432.CCR-07-1398. View

Lugli A, Tzankov A, Zlobec I, Terracciano L . Differential diagnostic and functional role of the multi-marker phenotype CDX2/CK20/CK7 in colorectal cancer stratified by mismatch repair status. Mod Pathol. 2008; 21(11):1403-12. DOI: 10.1038/modpathol.2008.117. View

McLeod H, Murray G . Tumour markers of prognosis in colorectal cancer. Br J Cancer. 1999; 79(2):191-203. PMC: 2362193. DOI: 10.1038/sj.bjc.6690033. View

Walsh M, Clendenning M, Williamson E, Pearson S, Walters R, Nagler B . Expression of MUC2, MUC5AC, MUC5B, and MUC6 mucins in colorectal cancers and their association with the CpG island methylator phenotype. Mod Pathol. 2013; 26(12):1642-56. DOI: 10.1038/modpathol.2013.101. View

10.

Lau S, Weiss L, Chu P . Differential expression of MUC1, MUC2, and MUC5AC in carcinomas of various sites: an immunohistochemical study. Am J Clin Pathol. 2004; 122(1):61-9. DOI: 10.1309/9R66-73QE-C06D-86Y4. View

11.

Manne U, Weiss H, Grizzle W . Racial differences in the prognostic usefulness of MUC1 and MUC2 in colorectal adenocarcinomas. Clin Cancer Res. 2000; 6(10):4017-25. View

12.

MOERTEL C, Fleming T, Macdonald J, Haller D, Laurie J, Goodman P . Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med. 1990; 322(6):352-8. DOI: 10.1056/NEJM199002083220602. View

13.

Lyall M, Dundas S, Curran S, Murray G . Profiling markers of prognosis in colorectal cancer. Clin Cancer Res. 2006; 12(4):1184-91. DOI: 10.1158/1078-0432.CCR-05-1864. View

14.

Jass J, Walsh M . Altered mucin expression in the gastrointestinal tract: a review. J Cell Mol Med. 2002; 5(3):327-51. PMC: 6517815. DOI: 10.1111/j.1582-4934.2001.tb00169.x. View

15.

Betge J, Kornprat P, Pollheimer M, Lindtner R, Schlemmer A, Rehak P . Tumor budding is an independent predictor of outcome in AJCC/UICC stage II colorectal cancer. Ann Surg Oncol. 2012; 19(12):3706-12. DOI: 10.1245/s10434-012-2426-z. View

16.

Owens S, Chiosea S, Kuan S . Selective expression of gastric mucin MUC6 in colonic sessile serrated adenoma but not in hyperplastic polyp aids in morphological diagnosis of serrated polyps. Mod Pathol. 2008; 21(6):660-9. DOI: 10.1038/modpathol.2008.55. View

17.

Corfield A, Carroll D, Myerscough N, Probert C . Mucins in the gastrointestinal tract in health and disease. Front Biosci. 2001; 6:D1321-57. DOI: 10.2741/corfield. View

18.

Khanh D, Mekata E, Mukaisho K, Sugihara H, Shimizu T, Shiomi H . Transmembrane mucin MUC1 overexpression and its association with CD10⁺ myeloid cells, transforming growth factor-β1 expression, and tumor budding grade in colorectal cancer. Cancer Sci. 2013; 104(7):958-64. PMC: 7657147. DOI: 10.1111/cas.12170. View

19.

Kocer B, Soran A, Erdogan S, Karabeyoglu M, Yildirim O, Eroglu A . Expression of MUC5AC in colorectal carcinoma and relationship with prognosis. Pathol Int. 2002; 52(7):470-7. DOI: 10.1046/j.1440-1827.2002.01369.x. View

20.

Baldus S, Monig S, Hanisch F, Zirbes T, Flucke U, Oelert S . Comparative evaluation of the prognostic value of MUC1, MUC2, sialyl-Lewis(a) and sialyl-Lewis(x) antigens in colorectal adenocarcinoma. Histopathology. 2002; 40(5):440-9. DOI: 10.1046/j.1365-2559.2002.01389.x. View