PIK3CAmutation is predictive of poor survival in patients with colorectal cancer

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Abstract
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, theK‐Rasmutation andPIK3CAmutation 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 ofPIK3CAmutation andK‐Rasmutation on AKT activation, and to clarify whetherPIK3CAmutation,K‐Rasmutation 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 ofK‐Rasand exons 9 and 20 ofPIK3CAwere 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,PIK3CAmutation 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,PIK3CAmutation 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 ofPIK3CAmutation in colorectal cancer patients. Patients withPIK3CAmutation should be followed up carefully. Moreover, our result suggests that inhibition ofPIK3CAmutant may be a new molecular target therapy.