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

Mod Pathol. 2013 Feb;26(2):302-13. doi: 10.1038/modpathol.2012.150. Epub 2012 Aug 31.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / metabolism
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-met / genetics*
  • Proto-Oncogene Proteins c-met / metabolism
  • Proto-Oncogene Proteins p21(ras)
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • ras Proteins / genetics*
  • ras Proteins / metabolism


  • KRAS protein, human
  • Nuclear Proteins
  • PI3KCA protein, human
  • Proto-Oncogene Proteins
  • Transcription Factors
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • PTEN Phosphohydrolase
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins