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High SMAD4 levels appear in MSI and hypermethylated colon cancers, and indicate a better prognosis
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.ORCID iD: 0000-0002-9933-2843
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
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2012 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 131, 779-788 p.Article in journal (Refereed) Published
Abstract [en]

Colorectal cancer (CRC) is one of the most common causes of cancer related deaths in western countries. CRC are commonly divided in cancers showing microsatellite stability (MSS) or microsatellite instability (MSI). A more novel classification is dependent on promoter hypermethylation of CpG islands (the CpG island methylator phenotype, CIMP), where cancers show high, low or negative methylation status. SMAD4, located on chromosome 18q, has been thoroughly investigated during the last years. Loss of SMAD4 expression has been reported to correlate with poor CRC patient prognosis. In this study we analyze the impact of SMAD4 expression on prognosis in relation to MSI screening status and CIMP status. 479 paraffin-embedded specimens of CRC were examined for nuclear SMAD4 expression using immunohistochemistry. The tumors were scored loss (-), moderate (+) and high (++) expressing tumors. Loss of SMAD4 correlated significantly with decreased survival in all colon cancer patients. High SMAD4 expression, on the other hand, was significantly associated with increased survival, especially in colon cancer patients which has undergone potential curative surgery. In addition, in MSI tumors and CIMP-high tumors, high SMAD4 expression was significantly related to increase in survival, while loss of SMAD4 resulted in a significantly poorer prognosis. SMAD4 expression was not correlated to prognosis in rectal cancer cases. We conclude, loss of SMAD4 indicates a poor prognosis in colon cancer patients. The novel findings that high SMAD4 expression predicts a better prognosis suggests that SMAD4 immunohistochemistry could constitute a prognostic marker in combination with CIMP and MSI screening status.

Place, publisher, year, edition, pages
Geneve: International union against cancer , 2012. Vol. 131, 779-788 p.
Keyword [en]
SMAD4, colon cancer, MSI, CIMP, high expression
National Category
Cancer and Oncology Microbiology
Research subject
URN: urn:nbn:se:umu:diva-49026DOI: 10.1002/ijc.26473PubMedID: 21964812OAI: diva2:452733
Available from: 2011-10-31 Created: 2011-10-31 Last updated: 2016-09-05Bibliographically approved

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Isaksson-Mettävainio, MartinPalmqvist, RichardDahlin, Anna MVan Guelpen, BethanyRutegård, JörgenÖberg, ÅkeHenriksson, Maria L
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International Journal of Cancer
Cancer and OncologyMicrobiology

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