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PIK3CA mutation is associated with poor prognosis among patients with curatively resected colon cancer.
- Source :
-
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2009 Mar 20; Vol. 27 (9), pp. 1477-84. Date of Electronic Publication: 2009 Feb 23. - Publication Year :
- 2009
-
Abstract
- Purpose: PIK3CA mutation and subsequent activation of the AKT pathway play an important role in colorectal carcinogenesis. However, little is known about the prognostic role of PIK3CA mutation in colon cancer.<br />Patients and Methods: Using 450 resectable colon cancers (stage I to III) in two independent prospective cohorts, we detected PIK3CA mutation in 82 tumors (18%) by pyrosequencing. Cox proportional hazards models were used to calculate hazard ratios (HRs) of colon cancer-specific and overall mortalities, adjusted for patient characteristics and tumoral molecular features, including the CpG island methylation phenotype, microsatellite instability (MSI), LINE-1 hypomethylation, and p53, CIMP, KRAS and BRAF mutation.<br />Results: Compared with patients with PIK3CA wild-type tumors, those with PIK3CA-mutated tumors experienced an increase in colon cancer-specific mortality according to univariate analysis (HR = 1.64; 95% CI, 0.95 to 2.86), which persisted after adjusting for other known or potential risk factors for cancer recurrence (including MSI; multivariate HR = 2.23; 95% CI, 1.21 to 4.11). The effect of PIK3CA mutation on cancer survival seemed to differ according to KRAS mutational status. Among patients with KRAS wild-type tumors, the presence of PIK3CA mutation was associated with a significant increase in colon cancer-specific mortality (HR = 3.80; 95% CI, 1.56 to 9.27). In contrast, PIK3CA mutation conferred no significant effect on mortality among patients with KRAS-mutated tumors (HR = 1.25; 95% CI, 0.52 to 2.96).<br />Conclusion: Among patients who undergo a curative resection of colon cancer, PIK3CA mutation is associated with shorter cancer-specific survival. The adverse effect of PIK3CA mutation may be potentially limited to patients with KRAS wild-type tumors.
- Subjects :
- Aged
Class I Phosphatidylinositol 3-Kinases
Colonic Neoplasms enzymology
Colonic Neoplasms pathology
Colonic Neoplasms surgery
Female
Genes, ras
Humans
Male
Mutation
Neoplasm Staging
Prognosis
Proto-Oncogene Proteins B-raf genetics
Biomarkers, Tumor genetics
Colonic Neoplasms genetics
Phosphatidylinositol 3-Kinases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1527-7755
- Volume :
- 27
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 19237633
- Full Text :
- https://doi.org/10.1200/JCO.2008.18.6544