Elsevier

Modern Pathology

Volume 26, Issue 2, February 2013, Pages 302-313
Modern Pathology

Article
Combined analysis of KRAS and PIK3CA mutations, MET and PTEN expression in primary tumors and corresponding metastases in colorectal cancer

https://doi.org/10.1038/modpathol.2012.150Get rights and content
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Abstract

Metastasis is the main cause of mortality in patients with colorectal cancer. However, most of the targeted therapies and predictive molecular biomarkers were developed based mainly on primary tumors. The current study was conducted to determine the degree of discordance between potential predictive and/or prognostic molecular markers in primary colorectal tumors and corresponding metastases, as this could have an impact on the efficacy of targeted therapies in the advanced colorectal cancer. KRAS, PIK3CA and BRAF mutations were determined by Sanger sequencing and mutant-enriched polymerase chain reaction (PCR) assays in 83 paired samples, MET gene copy number by quantitative PCR in 59, MET expression by immunohistochemistry in 73 and nuclear and cytoplasmic expression of PTEN by immunohistochemistry in 78 and 71 pairs, respectively. A certain degree of discordance between primary tumors and corresponding metastases was demonstrated for all examined biomarkers except BRAF mutations. PIK3CA exon 9 mutations in primary tumors and loss of PTEN nuclear expression in metastases correlated with KRAS mutations. KRAS wild-type status in primary tumors was associated with loss of PTEN cytoplasmic expression and high gene copy number of MET. Survival and clinical data were available for 68 patients. The multiple regression analysis revealed that the right-sided tumor localization and overexpression of MET were associated with shorter overall survival.

Keywords

colorectal cancer
KRAS
MET amplification
PIK3CA and BRAF mutations
primary tumor and corresponding metastasis
PTEN and MET expression by immunohistochemistry

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Supplementary Information accompanies the paper on Modern Pathology website

Alexandra Voutsina and Maria Tzardi: These authors contributed equally to this work.

Supplementary information

The online version of this article (doi:10.1038/modpathol.2012.150) contains supplementary material, which is available to authorized users.