title: Combined analysis of KRAS and PIK3CA mutations, MET and PTEN expression in primary tumors and corresponding metastases in colorectal cancer.
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.
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Greece. voutsina@med.uoc.gr
authors.forename: Alexandra
authors.initials: A
authors.lastname: Voutsina
authors.forename: Maria
authors.initials: M
authors.lastname: Tzardi
authors.forename: Aristea
authors.initials: A
authors.lastname: Kalikaki
authors.forename: Zafeiris
authors.initials: Z
authors.lastname: Zafeiriou
authors.forename: Elsa
authors.initials: E
authors.lastname: Papadimitraki
authors.forename: Michael
authors.initials: M
authors.lastname: Papadakis
authors.forename: Dimitris
authors.initials: D
authors.lastname: Mavroudis
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C117307:KRAS protein, human; D009687:Nuclear Proteins; C503859:PI3KCA protein, human; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D051059:PTEN Phosphohydrolase; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins