title: Mutation of thePIK3CAgene as a prognostic factor in patients with colorectal cancer.
abstract: Colorectal cancer (CRC) is one of the most common cancers worldwide, with ~700,000 mortalities occurring due to CRC in 2012. The treatment options are effective in a small percentage of patients, and it is important to identify specific biomarkers in order to determine patients for whom the available therapies will be beneficial. It has been hypothesised that thePIK3CAgene mutation may affect the response to therapy of patients with metastatic CRC. In the present study, primary tumour specimens were collected from 156 patients with CRC who were treated in the Military Institute of Medicine in Warsaw (Warsaw, Poland). Codons 12 and 13 of exon 1 ofKRAS, exons 11 and 15 ofBRAFand exons 9 and 20 ofPIK3CAwere analysed for mutation using direct sequencing. The prognostic value of each mutation and the clinical and pathological variables of these tumours were estimated. The results revealed thatPIK3CAmutations were present in 15 patients (9.6%), of whom seven (46.7%) possessed mutations in codon 9 and eight (53.3%) possessed mutations in codon 20. Mutation in thePIK3CAgene was detected in six patients withKRASgene mutations, which accounted for 40% ofPIK3CA-mutated tumours, and in one patient withBRAFmutations, which accounted for 6.6% ofPIK3CA-mutated tumours. No significant differences were identified between the overall survival (OS) rates of patients withPIK3CAmutations (median OS, 56.7 months) and those with wild-typePIK3CAgenes (median OS, 47.6 months) (P=0.1270). Univariate analysis identified that the following prognostic factors affected the OS rate in the current patient cohort: Gender, female patients survived for 57.5 months compared with 39.3 months for male patients (P=0.0111); and lymph node involvement grade, as survival of patients without lymph node metastases was 61.4 months compared with 45.4 months in patients presenting with metastases (P=0.0122). The findings of the present analysis indicate thatPIK3CAmutation status is not a prognostic factor in CRC patients. In addition, no statistically significant association exists between tumours withPIK3CAmutations and clinical or pathological factors.
authors.affiliation: Department of Oncology, Military Institute of Medicine, Warsaw 04-141, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Stec
authors.affiliation: Department of Oncology, Military Institute of Medicine, Warsaw 04-141, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Semeniuk-Wojtaś
authors.affiliation: Department of Clinical Molecular Biology, Medical University of Bialystok, Bialystok 15-089, Poland.
authors.forename: Radosław
authors.initials: R
authors.lastname: Charkiewicz
authors.affiliation: Department of Oncology, Military Institute of Medicine, Warsaw 04-141, Poland.
authors.forename: Lubomir
authors.initials: L
authors.lastname: Bodnar
authors.affiliation: Department of Oncology, Military Institute of Medicine, Warsaw 04-141, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Korniluk
authors.affiliation: Department of Oncology, Military Institute of Medicine, Warsaw 04-141, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Smoter
authors.affiliation: Department of Clinical Pathology, Medical University of Bialystok, Bialystok 15-089, Poland.
authors.forename: Lech
authors.initials: L
authors.lastname: Chyczewski
authors.affiliation: Department of Clinical Molecular Biology, Medical University of Bialystok, Bialystok 15-089, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Nikliński
authors.affiliation: Department of Oncology, Military Institute of Medicine, Warsaw 04-141, Poland.
authors.forename: Cezary
authors.initials: C
authors.lastname: Szczylik
keywords: colorectal cancer; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha mutations; prognostic factor