title: Gene expression of the mismatch repair gene MSH2 in primary colorectal cancer.
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.
authors: Danish Colorectal Cancer Group South, University of Southern Denmark and Vejle Hospital, Vejle, Denmark. Lars.Henrik.Jensen@slb.regionsyddanmark.dk
authors: Lars Henrik
authors: LH
authors: Jensen
authors: Hidekazu
authors: H
authors: Kuramochi
authors: Dorthe Gylling
authors: DG
authors: Crüger
authors: Jan
authors: J
authors: Lindebjerg
authors: Steen
authors: S
authors: Kolvraa
authors: Peter
authors: P
authors: Danenberg
authors: Kathleen
authors: K
authors: Danenberg
authors: Anders
authors: A
authors: Jakobsen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000096:biosynthesis* / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein