Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Clinical Pathology
Published in: BMC Clinical Pathology 1/2017

Open Access 01-12-2017 | Research article

Differential expression of CK20, β-catenin, and MUC2/5AC/6 in Lynch syndrome and familial colorectal cancer type X

Authors: Stefan Haraldsson, Louise Klarskov, Mef Nilbert, Inge Bernstein, Jesper Bonde, Susanne Holck

Published in: BMC Clinical Pathology | Issue 1/2017

Login to get access

Abstract

Background

Hereditary non-polyposis colorectal cancer comprises Lynch syndrome and familial colorectal cancer type X (FCCTX). Differences in genetics, demographics and histopathology have been extensively studied. The purpose of this study is to characterize their immunoprofile of markers other than MMR proteins.

Methods

We compared the expression patterns of cytokeratins (CK7 and CK20), mucins (MUC2/5 AC/6), CDX2 and β-catenin in Lynch syndrome and FCCTX.

Results

Differences were identified for CK20 and nuclear β-catenin, which were significantly more often expressed in FCCTX than in Lynch syndrome (p < 0.001), whereas MUC2, MUC5AC and MUC6 were overexpressed in Lynch syndrome tumors compared with FCCTX tumors (p = 0.001, < 0.01, and < 0.001, respectively). We observed no differences in the expression patterns of CK7 and CDX2.

Conclusions

In summary, we identified significant differences in the immunoprofiles of colorectal cancers linked to FCCTX and Lynch syndrome with a more sporadic-like profile in the former group and a more distinct profile with frequent MUC6 positivity in the latter group.
Literature
1.
Lindor NM, Rabe K, Petersen GM, Haile R, Casey G, Baron J, Gallinger S, Bapat B, Aronson M, Hopper J, et al. Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X. JAMA. 2005;293(16):1979–85.CrossRefPubMedPubMedCentral
2.
Vasen HF, Mecklin JP, Khan PM, Lynch HT. The international collaborative group on hereditary non-polyposis colorectal cancer (ICG-HNPCC). Dis Colon Rectum. 1991;34(5):424–5.CrossRefPubMed
3.
Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, lynch syndrome) proposed by the international collaborative group on HNPCC. Gastroenterology. 1999;116(6):1453–6.CrossRefPubMed
4.
Klarskov L, Holck S, Bernstein I, Nilbert M. Hereditary colorectal cancer diagnostics: morphological features of familial colorectal cancer type X versus lynch syndrome. J Clin Pathol. 2012;65(4):352–6.CrossRefPubMed
5.
Halvarsson B, Muller W, Planck M, Benoni AC, Mangell P, Ottosson J, Hallen M, Isinger A, Nilbert M. Phenotypic heterogeneity in hereditary non-polyposis colorectal cancer: identical germline mutations associated with variable tumour morphology and immunohistochemical expression. J Clin Pathol. 2007;60(7):781–6.CrossRefPubMed
6.
Jenkins MA, Hayashi S, O'Shea AM, Burgart LJ, Smyrk TC, Shimizu D, Waring PM, Ruszkiewicz AR, Pollett AF, Redston M, et al. Pathology features in Bethesda guidelines predict colorectal cancer microsatellite instability: a population-based study. Gastroenterology. 2007;133(1):48–56.CrossRefPubMedPubMedCentral
7.
Laurent C, Svrcek M, Flejou JF, Chenard MP, Duclos B, Freund JN, Reimund JM. Immunohistochemical expression of CDX2, beta-catenin, and TP53 in inflammatory bowel disease-associated colorectal cancer. Inflamm Bowel Dis. 2011;17(1):232–40.CrossRefPubMed
8.
Bayrak R, Yenidunya S, Haltas H. Cytokeratin 7 and cytokeratin 20 expression in colorectal adenocarcinomas. Pathol Res Pract. 2011;207(3):156–60.CrossRefPubMed
9.
McGregor DK, Wu TT, Rashid A, Luthra R, Hamilton SR. Reduced expression of cytokeratin 20 in colorectal carcinomas with high levels of microsatellite instability. Am J Surg Pathol. 2004;28(6):712–8.CrossRefPubMed
10.
Olsen AK, Coskun M, Bzorek M, Kristensen MH, Danielsen ET, Jorgensen S, Olsen J, Engel U, Holck S, Troelsen JT. Regulation of APC and AXIN2 expression by intestinal tumor suppressor CDX2 in colon cancer cells. Carcinogenesis. 2013;34(6):1361–9.CrossRefPubMed
11.
Yao T, Tsutsumi S, Akaiwa Y, Takata M, Nishiyama K, Kabashima A, Tsuneyoshi M. Phenotypic expression of colorectal adenocarcinomas with reference to tumor development and biological behavior. Gann. 2001;92(7):755–61.PubMed
12.
Francisco I, Albuquerque C, Lage P, Belo H, Vitoriano I, Filipe B, Claro I, Ferreira S, Rodrigues P, Chaves P, et al. Familial colorectal cancer type X syndrome: two distinct molecular entities? Familial Cancer. 2011;10(4):623–31.CrossRefPubMed
13.
Sanchez-Tome E, Rivera B, Perea J, Pita G, Rueda D, Mercadillo F, Canal A, Gonzalez-Neira A, Benitez J, Urioste M. Genome-wide linkage analysis and tumoral characterization reveal heterogeneity in familial colorectal cancer type X. J Gastroenterol. 2015;50(6):657–66.CrossRefPubMed
14.
Chu PG, Weiss LM. Keratin expression in human tissues and neoplasms. Histopathology. 2002;40(5):403–39.CrossRefPubMed
15.
Kim MJ, Hong SM, Jang SJ, Yu E, Kim JS, Kim KR, Gong G, Ro JY. Invasive colorectal micropapillary carcinoma: an aggressive variant of adenocarcinoma. Hum Pathol. 2006;37(7):809–15.CrossRefPubMed
16.
Lagendijk JH, Mullink H, van Diest PJ, Meijer GA, Meijer CJ. Immunohistochemical differentiation between primary adenocarcinomas of the ovary and ovarian metastases of colonic and breast origin. Comparison between a statistical and an intuitive approach. J Clin Pathol. 1999;52(4):283–90.CrossRefPubMedPubMedCentral
17.
Lee MJ, Lee HS, Kim WH, Choi Y, Yang M. Expression of mucins and cytokeratins in primary carcinomas of the digestive system. Mod Pathol. 2003;16(5):403–10.CrossRefPubMed
18.
Moll R, Lowe A, Laufer J, Franke WW. Cytokeratin 20 in human carcinomas. A new histodiagnostic marker detected by monoclonal antibodies. Am J Pathol. 1992;140(2):427–47.PubMedPubMedCentral
19.
Park SY, Kim HS, Hong EK, Kim WH. Expression of cytokeratins 7 and 20 in primary carcinomas of the stomach and colorectum and their value in the differential diagnosis of metastatic carcinomas to the ovary. Hum Pathol. 2002;33(11):1078–85.CrossRefPubMed
20.
Tot T. The role of cytokeratins 20 and 7 and estrogen receptor analysis in separation of metastatic lobular carcinoma of the breast and metastatic signet ring cell carcinoma of the gastrointestinal tract. APMIS. 2000;108(6):467–72.CrossRefPubMed
21.
Omary MB, Ku NO, Strnad P, Hanada S. Toward unraveling the complexity of simple epithelial keratins in human disease. J Clin Invest. 2009;119(7):1794–805.CrossRefPubMedPubMedCentral
22.
Saad RS, Silverman JF, Khalifa MA, Rowsell C. CDX2, cytokeratins 7 and 20 immunoreactivity in rectal adenocarcinoma. Appl Immunohistochem Mol Morphol. 2009;17(3):196–201.CrossRefPubMed
23.
Barbareschi M, Murer B, Colby TV, Chilosi M, Macri E, Loda M, Doglioni C. CDX-2 homeobox gene expression is a reliable marker of colorectal adenocarcinoma metastases to the lungs. Am J Surg Pathol. 2003;27(2):141–9.CrossRefPubMed
24.
Pancione M, Di Blasi A, Sabatino L, Fucci A, Dalena AM, Palombi N, Carotenuto P, Aquino G, Daniele B, Normanno N, et al. A novel case of rhabdoid colon carcinoma associated with a positive CpG island methylator phenotype and BRAF mutation. Hum Pathol. 2011;42(7):1047–52.CrossRefPubMed
25.
Dalerba P, Sahoo D, Paik S, Guo X, Yothers G, Song N, Wilcox-Fogel N, Forgo E, Rajendran PS, Miranda SP, et al. CDX2 as a prognostic biomarker in stage II and stage III colon cancer. N Engl J Med. 2016;374(3):211–22.CrossRefPubMedPubMedCentral
26.
Logani S, Oliva E, Arnell PM, Amin MB, Young RH. Use of novel immunohistochemical markers expressed in colonic adenocarcinoma to distinguish primary ovarian tumors from metastatic colorectal carcinoma. Mod Pathol. 2005;18(1):19–25.CrossRefPubMed
27.
Moskaluk CA, Zhang H, Powell SM, Cerilli LA, Hampton GM, Frierson HF Jr. Cdx2 protein expression in normal and malignant human tissues: an immunohistochemical survey using tissue microarrays. Mod Pathol. 2003;16(9):913–9.CrossRefPubMed
28.
Werling RW, Yaziji H, Bacchi CE, Gown AM. CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas. Am J Surg Pathol. 2003;27(3):303–10.CrossRefPubMed
29.
Baba Y, Nosho K, Shima K, Freed E, Irahara N, Philips J, Meyerhardt JA, Hornick JL, Shivdasani RA, Fuchs CS, et al. Relationship of CDX2 loss with molecular features and prognosis in colorectal cancer. Clin Cancer Res. 2009;15(14):4665–73.CrossRefPubMedPubMedCentral
30.
Lugli A, Tzankov A, Zlobec I, Terracciano LM. 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.CrossRefPubMed
31.
Messerini L, Vitelli F, De Vitis LR, Mori S, Calzolari A, Palmirotta R, Calabro A, Papi L. Microsatellite instability in sporadic mucinous colorectal carcinomas: relationship to clinico-pathological variables. J Pathol. 1997;182(4):380–4.CrossRefPubMed
32.
Shin JH, Bae JH, Lee A, Jung CK, Yim HW, Park JS, Lee KY. CK7, CK20, CDX2 and MUC2 Immunohistochemical staining used to distinguish metastatic colorectal carcinoma involving ovary from primary ovarian mucinous adenocarcinoma. Jpn J Clin Oncol. 2010;40(3):208–13.CrossRefPubMed
33.
Ishizu H, Kumagai J, Eishi Y, Takizawa T, Koike M. Mucin core protein expression by colorectal mucinous carcinomas with or without mucus hyperplasia. J Gastroenterol. 2004;39(2):125–32.CrossRefPubMed
34.
Chu PG, Chung L, Weiss LM, Lau SK. Determining the site of origin of mucinous adenocarcinoma: an immunohistochemical study of 175 cases. Am J Surg Pathol. 2011;35(12):1830–6.CrossRefPubMed
35.
Leir SH, Harris A. MUC6 mucin expression inhibits tumor cell invasion. Exp Cell Res. 2011;317(17):2408–19.CrossRefPubMed
36.
Betge J, Schneider NI, Harbaum L, Pollheimer MJ, Lindtner RA, Kornprat P, Ebert MP, Langner C. MUC1, MUC2, MUC5AC, and MUC6 in colorectal cancer: expression profiles and clinical significance. Virchows Arch. 2016;469(3):255–65.CrossRefPubMedPubMedCentral
37.
Fujimoto Y, Nakanishi Y, Sekine S, Yoshimura K, Akasu T, Moriya Y, Shimoda T. CD10 expression in colorectal carcinoma correlates with liver metastasis. Dis Colon Rectum. 2005;48(10):1883–9.CrossRefPubMed
38.
Hao X, Frayling IM, Willcocks TC, Han W, Tomlinson IP, Pignatelli MN, Pretlow TP, Talbot IC. Beta-catenin expression and allelic loss at APC in sporadic colorectal carcinogenesis. Virchows Arch. 2002;440(4):362–6.CrossRefPubMed
39.
Lugli A, Zlobec I, Minoo P, Baker K, Tornillo L, Terracciano L, Jass JR. Prognostic significance of the wnt signalling pathway molecules APC, beta-catenin and E-cadherin in colorectal cancer: a tissue microarray-based analysis. Histopathology. 2007;50(4):453–64.CrossRefPubMed
40.
Abdel-Rahman WM, Ollikainen M, Kariola R, Jarvinen HJ, Mecklin JP, Nystrom-Lahti M, Knuutila S, Peltomaki P. Comprehensive characterization of HNPCC-related colorectal cancers reveals striking molecular features in families with no germline mismatch repair gene mutations. Oncogene. 2005;24(9):1542–51.CrossRefPubMed
41.
Sanchez-de-Abajo A, de la Hoya M, van Puijenbroek M, Tosar A, Lopez-Asenjo JA, Diaz-Rubio E, Morreau H, Caldes T. Molecular analysis of colorectal cancer tumors from patients with mismatch repair proficient hereditary nonpolyposis colorectal cancer suggests novel carcinogenic pathways. Clin Cancer Res. 2007;13(19):5729–35.CrossRefPubMed
42.
Balaz P, Plaschke J, Kruger S, Gorgens H, Schackert HK. TCF-3, 4 protein expression correlates with beta-catenin expression in MSS and MSI-H colorectal cancer from HNPCC patients but not in sporadic colorectal cancers. Int J Color Dis. 2010;25(8):931–9.CrossRef
43.
Isinger-Ekstrand A, Therkildsen C, Bernstein I, Nilbert M. Deranged Wnt signaling is frequent in hereditary nonpolyposis colorectal cancer. Familial Cancer. 2011;10(2):239–43.CrossRefPubMed
44.
Dominguez-Valentin M, Therkildsen C, Veerla S, Jonsson M, Bernstein I, Borg A, Nilbert M. Distinct gene expression signatures in lynch syndrome and familial colorectal cancer type x. PLoS One. 2013;8(8):e71755.CrossRefPubMedPubMedCentral
45.
Dominguez-Valentin M, Therkildsen C, Da Silva S, Nilbert M. Familial colorectal cancer type X: genetic profiles and phenotypic features. Mod Pathol. 2015;28(1):30–6.CrossRefPubMed
Metadata
Title
Differential expression of CK20, β-catenin, and MUC2/5AC/6 in Lynch syndrome and familial colorectal cancer type X
Authors
Stefan Haraldsson
Louise Klarskov
Mef Nilbert
Inge Bernstein
Jesper Bonde
Susanne Holck
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Clinical Pathology / Issue 1/2017
Electronic ISSN: 1472-6890
DOI
https://doi.org/10.1186/s12907-017-0052-1

Other articles of this Issue 1/2017

BMC Clinical Pathology 1/2017 Go to the issue

Research article

Accuracy of cervical cytology: comparison of diagnoses of 100 Pap smears read by four pathologists at three hospitals in Norway

Research article

High expression of EphA3 (erythropoietin-producing hepatocellular A3) in gastric cancer is associated with metastasis and poor survival

Research article

Impending relapse of myelodysplastic syndrome after allogeneic transplant is difficult to diagnose and requires a multi-modal approach

Case report

Lymphoepithelial carcinoma: a case report of a rare tumor of the larynx

Research article

Peritumoral lymphatic vessel density and invasion detected with immunohistochemical marker D240 is strongly associated with distant metastasis in breast carcinoma

Research article

Cerebrospinal fluid pleocytosis level as a diagnostic predictor? A cross-sectional study
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits