Clinicopathological characteristics, microsatellite instability, and expression of mucin core proteins and p53 in colorectal mucinous adenocarcinomas in relation to location
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It has been suggested that right-sided and left-sided colorectal cancer may arise by different mechanisms. However, there have been few studies of mucinous adenocarcinoma (MA) in relation to location. Therefore, we analyzed clinicopathological characteristics, microsatellite instability (MSI), and expression of MUC1, MUC2, MUC5AC mucin core proteins, and p53 by immunohistochemistry in relation to tumor location. Ninety-six consecutive colorectal MAs and ninety-eight nonmucinous adenocarcinomas (nMAs) were investigated. Right-sided MAs, by comparison with those on the left side, were characterized by older age, larger tumor size, lower stage at presentation, peritumoral lymphocytic response, background of serrated adenoma, MSI-H phenotype, higher MUC2 and MUC5AC expression, and lower p53 protein overexpression. Right-sided nMAs, relative to those on the left side, were associated with MSI-H phenotype, higher MUC2 and MUC5AC expression, and lower p53 protein overexpression. Thus, MSI-H phenotype, expression of MUC2 and MUC5AC, and infrequent p53 protein overexpression are associated with right-sided location as well as mucinous histology. In univariate analysis, right-sided location had a favorable effect on disease specific survival of the patients with MA, although it is not an independent predictor of survival. Our results indicate that MA is a distinctive form of colorectal cancer and has different phenotypes depending on tumor location.
KeywordsMucinous adenocarcinoma Tumor location Microsatellite instability MUC2 MUC5AC
This work is supported by a grant from the Seoul National University Bundang Hospital Research Fund, Seongnam, Korea. So Yeon Park and Hye Seung Lee contributed equally to this work.
- 2.Baldus SE, Monig SP, Huxel S, Landsberg S, Hanisch FG, Engelmann K, Schneider PM, Thiele J, Holscher AH, Dienes HP (2004) MUC1 and nuclear beta-catenin are coexpressed at the invasion front of colorectal carcinomas and are both correlated with tumor prognosis. Clin Cancer Res 10:2790–2796PubMedCrossRefGoogle Scholar
- 3.Biemer-Huttmann AE, Walsh MD, McGuckin MA, Ajioka Y, Watanabe H, Leggett BA, Jass JR (1999) Immunohistochemical staining patterns of MUC1, MUC2, MUC4, and MUC5AC mucins in hyperplastic polyps, serrated adenomas, and traditional adenomas of the colorectum. J Histochem Cytochem 47:1039–1048PubMedGoogle Scholar
- 5.de Jong AE, van Puijenbroek M, Hendriks Y, Tops C, Wijnen J, Ausems MG, Meijers-Heijboer H, Wagner A, van Os TA, Brocker-Vriends AH, Vasen HF, Morreau H (2004) Microsatellite instability, immunohistochemistry, and additional PMS2 staining in suspected hereditary nonpolyposis colorectal cancer. Clin Cancer Res 10:972–980PubMedCrossRefGoogle Scholar
- 8.Glebov OK, Rodriguez LM, Nakahara K, Jenkins J, Cliatt J, Humbyrd CJ, DeNobile J, Soballe P, Simon R, Wright G, Lynch P, Patterson S, Lynch H, Gallinger S, Buchbinder A, Gordon G, Hawk E, Kirsch IR (2003) Distinguishing right from left colon by pattern of gene expression. Cancer Epidemiol Biomarkers Prev 12:755–762PubMedGoogle Scholar
- 9.Green FL, Balch CM, Fleming ID, Fritz AG, Balch CM, Haller DG, Morrow M (eds) (2002) AJCC cancer staging manual, 6th edn. Springer, Berlin Heidelberg New YorkGoogle Scholar
- 10.Greenson JK, Bonner JD, Ben-Yzhak O, Cohen HI, Miselevich I, Resnick MB, Trougouboff P, Tomsho LD, Kim E, Low M, Almog R, Rennert G, Gruber SB (2003) Phenotype of microsatellite unstable colorectal carcinomas: Well-differentiated and focally mucinous tumors and the absence of dirty necrosis correlate with microsatellite instability. Am J Surg Pathol 27:563–570PubMedCrossRefGoogle Scholar
- 17.Kazama Y, Watanabe T, Kanazawa T, Tada T, Tanaka J, Nagawa H (2005) Mucinous carcinomas of the colon and rectum show higher rates of microsatellite instability and lower rates of chromosomal instability: a study matched for T classification and tumor location. Cancer 103:2023–2029PubMedCrossRefGoogle Scholar
- 21.Losi L, Scarselli A, Benatti P, Ponz de Leon M, Roncucci L, Pedroni M, Borghi F, Lamberti I, Rossi G, Marino M, Ponti G, Zangardi G, Menigatti M, Di Gregorio C (2004) Relationship between MUC5AC and altered expression of MLH1 protein in mucinous and nonmucinous colorectal carcinomas. Pathol Res Pract 200:371–377PubMedCrossRefGoogle Scholar
- 26.Plaschke J, Kruger S, Pistorius S, Theissig F, Saeger HD, Schackert HK (2002) Involvement of hMSH6 in the development of hereditary and sporadic colorectal cancer revealed by immunostaining is based on germline mutations, but rarely on somatic inactivation. Int J Cancer 97:643–648PubMedCrossRefGoogle Scholar
- 27.Rigau V, Sebbagh N, Olschwang S, Paraf F, Mourra N, Parc Y, Flejou JF (2003) Microsatellite instability in colorectal carcinoma. The comparison of immunohistochemistry and molecular biology suggests a role for hMSH6 [correction of hMLH6] immunostaining. Arch Pathol Lab Med 127:694–700PubMedGoogle Scholar
- 35.Young J, Simms LA, Biden KG, Wynter C, Whitehall V, Karamatic R, George J, Goldblatt J, Walpole I, Robin SA, Borten MM, Stitz R, Searle J, McKeone D, Fraser L, Purdie DR, Podger K, Price R, Buttenshaw R, Walsh MD, Barker M, Leggett BA, Jass JR (2001) Features of colorectal cancers with high-level microsatellite instability occurring in familial and sporadic settings: parallel pathways of tumorigenesis. Am J Pathol 159:2107–2116PubMedGoogle Scholar