Tumor Biology

, Volume 32, Issue 5, pp 977–983 | Cite as

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

  • Lars Henrik Jensen
  • Hidekazu Kuramochi
  • Dorthe Gylling Crüger
  • Jan Lindebjerg
  • Steen Kolvraa
  • Peter Danenberg
  • Kathleen Danenberg
  • Anders Jakobsen
Research Article

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.

Keywords

Colorectal cancer Mismatch repair MSH2 Gene expression qPCR Methods MSI 

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2011

Authors and Affiliations

  • Lars Henrik Jensen
    • 1
    • 4
  • Hidekazu Kuramochi
    • 2
  • Dorthe Gylling Crüger
    • 1
  • Jan Lindebjerg
    • 1
  • Steen Kolvraa
    • 1
  • Peter Danenberg
    • 2
  • Kathleen Danenberg
    • 3
  • Anders Jakobsen
    • 1
  1. 1.Danish Colorectal Cancer Group SouthUniversity of Southern Denmark and Vejle HospitalVejleDenmark
  2. 2.Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer CenterUniversity of Southern CaliforniaLos AngelesUSA
  3. 3.Response GeneticsLos AngelesUSA
  4. 4.Department of Oncology Vejle HospitalVejleDenmark

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