Document Detail


PIK3CA mutation is predictive of poor survival in patients with colorectal cancer.
MedLine Citation:
PMID:  17590872     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The PI3K-AKT pathway is activated in a variety of human cancers, resulting in disturbance of cell growth, proliferation and survival. Among the factors affecting the pathway, the K-Ras mutation and PIK3CA mutation are the most common oncogenic alterations in colorectal cancer. We hypothesized that these two mutations are important in activation of the PI3K pathway and colorectal carcinogenesis. In this study, we aimed to examine the influence of PIK3CA mutation and K-Ras mutation on AKT activation, and to clarify whether PIK3CA mutation, K-Ras mutation and p-AKT expression may be used as parameters for predicting prognosis in colorectal cancer. Tissue samples from 158 colorectal cancer patients who underwent surgical resection were examined. The sequences of exon 1 of K-Ras and exons 9 and 20 of PIK3CA were determined by direct sequencing using genomic DNA extracted from paraffin-embedded blocks. Activation status of AKT was evaluated by immunohistochemical staining using phospho-specific AKT antibody (Ser473). Correlation between these factors and clinicopathologic findings/patient survival were examined. As a result, PIK3CA mutation was significantly associated with shorter relapse-free survival (RFS) in stage II/III patients (p = 0.0216) and shorter disease-specific survival in all patients (p = 0.0357). In the multivariate analysis, PIK3CA mutation was the only independent and significant prognostic factor for RFS in stage II/III patients (p = 0.0433, HR 2.478). This study revealed the prognostic value of PIK3CA mutation in colorectal cancer patients. Patients with PIK3CA mutation should be followed up carefully. Moreover, our result suggests that inhibition of PIK3CA mutant may be a new molecular target therapy.
Authors:
Shunsuke Kato; Satoru Iida; Tetsuro Higuchi; Toshiaki Ishikawa; Yoko Takagi; Masamichi Yasuno; Masayuki Enomoto; Hiroyuki Uetake; Kenichi Sugihara
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  121     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-08-27     Completed Date:  2007-10-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1771-8     Citation Subset:  IM    
Copyright Information:
(c) 2007 Wiley-Liss, Inc.
Affiliation:
Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. s-katou@daiichi.or.jp
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / genetics*
Aged
Analysis of Variance
Colorectal Neoplasms / genetics*,  mortality*
Female
Genes, ras*
Humans
Male
Middle Aged
Mutation*
Predictive Value of Tests
Prognosis
Survival Analysis
Tumor Markers, Biological / genetics*
Chemical
Reg. No./Substance:
0/Tumor Markers, Biological; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.1.137/PIK3CA protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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