Expression of Phosphoinositide 3-Kinase p110α and p110β Subunits and PIK3CA Mutation in Patients With Advanced Gastric Carcinoma

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Abstract

Activation of phosphoinositide 3-kinase (PI3K) is pivotal for the activity of the oncogenic PI3K/AKT signaling pathway. This study assessed the expression of 2 PI3K isoform proteins, p110α and p110β, and PIK3CA mutational status in advanced gastric carcinoma (AGC) and their correlation with clinicopathologic factors. Tissue microarray blocks were generated from 99 AGCs and immunohistochemically stained for p110α and p110β. Analysis of mutations in the PIK3CA gene, which encodes p110α, was performed using the PNAClamp PIK3CA Mutation Detection kit. Of the 99 tumors, positivity was seen in 62 (62.6%) for p110α and 97 (98.0%) for p110β with variable intensity and extent of staining. The median H-scores were 40 (range: 0 to 300) for p110α and 180 (range: 0 to 300) for p110β. Isoform p110α was more highly expressed in tumors with a lower pathologic T stage (P=0.035) and TNM stage (P=0.165), while p110β was not significantly associated with clinicopathologic factors. Samples with high p110α expression had a trend toward longer overall survival (OS) although it was not statistically significant (P=0.271), whereas high p110β expression correlated with shorter OS (P=0.016). In addition, p110β was an independent factor for poor prognosis in multivariate analysis for OS. Eight (8.1%) samples had PIK3CA mutations in exon 9. Mutational status at this locus was not significantly correlated with clinicopathologic factors. These results imply that p110β could have a more important role in the progression and aggressiveness of AGC than p110α and has potential as a prognostic biomarker in patients with AGC.

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