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Gene expression of the mismatch repair gene MSH2 in primary colorectal cancer

  • Research Article
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Tumor Biology

Abstract

Microsatellite instability (MSI) is caused by defective mismatch repair (MMR) and is one of the very few molecular markers with proven clinical importance in colorectal cancer with respect to heredity, prognosis, and treatment effect. The gene expression of the MMR gene MSH2 may be a quantitative marker for the level of MMR and a potential molecular marker with clinical relevance. The aim was to investigate the gene expression of MSH2 in primary operable colorectal cancer in correlation with MSI, protein expression, and promoter hypermethylation. In a cohort of 210 patients, the primary tumor and lymphnode metastases were analyzed with immunohistochemistry, methylation and MSI analyses, and quantitative polymerase chain reaction (PCR). The median gene expression of MSH2 was 1.00 (range 0.16–11.2, quartiles 0.70–1.51) and there was good agreement between the gene expression in primary tumor and lymph node metastasis (Spearman’s rho = 0.57, p < 0.001, n = 73). The validity of gene expression analysis was made probable by a significant correlation to protein expression (p = 0.005). MSI was most often caused by deficient MLH1 and was not correlated to MSH2 expression. Hypermethylation of the MSH2 gene promoter was only detected in 14 samples and only at a low level with no correlation to gene expression. MSH2 gene expression was not a prognostic factor for overall survival in univariate or multivariate analysis. The gene expression of MSH2 is a potential quantitative marker ready for further clinical validation.

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Conflicts of interest

Kathleen D. Danenberg, Response Genetics, leadership role (CEO), stock ownership. Peter V. Danenberg, Response Genetics, advisory role, stock ownership. Response Genetics funded the gene expression analysis. Other analyses were funded by Vejle Hospital and the region of Southern Denmark.

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Authors and Affiliations

  1. Danish Colorectal Cancer Group South, University of Southern Denmark and Vejle Hospital, Vejle, Denmark

    Lars Henrik Jensen, Dorthe Gylling Crüger, Jan Lindebjerg, Steen Kolvraa & Anders Jakobsen

  2. Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA

    Hidekazu Kuramochi & Peter Danenberg

  3. Response Genetics, Los Angeles, CA, USA

    Kathleen Danenberg

  4. Department of Oncology Vejle Hospital, 25 Kabbeltoft, 7100, Vejle, Denmark

    Lars Henrik Jensen

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  1. Lars Henrik Jensen
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  2. Hidekazu Kuramochi
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  3. Dorthe Gylling Crüger
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Correspondence to Lars Henrik Jensen.

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Jensen, L.H., Kuramochi, H., Crüger, D.G. et al. Gene expression of the mismatch repair gene MSH2 in primary colorectal cancer. Tumor Biol. 32, 977–983 (2011). https://doi.org/10.1007/s13277-011-0199-9

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  • DOI: https://doi.org/10.1007/s13277-011-0199-9

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