Abstract
present in 53 cases (24%) and was significantly correlated with deeper invasion (p=0.02). IGF1R was positive in 62 cases (29%) and was significantly correlated with intestinal histological type (p=0.03) and MSI (p=0.01). Although pAkt expression was only correlated with HER2 overexpression (p=0.005), pAkt expression was more frequent in cases with PIK3CA exon 20 mutations (100%) than in those with other PIK3CA mutations (50%). In multivariable analysis of prognostic factors, male, Stage 3 or 4, PTEN inactivation and pAkt expression were significantly correlated with poor prognosis. Among themolecular alterations analyzed in this study, 90 cases (43%) showed a single alteration and 32 cases (15%) showed two or more alterations. With increase in the number of alterations, frequency of pAkt expression tended to increase and prognosis tended to be worse. p95HER2 expression was positive in 13 (34%) of 38 HER2-positive cases. The 3-year survival rate of patients with p95HER2 positive was shorter than that of other patients (48% vs 68%). Conclusions: The number of alterations in each patient was significantly correlated with poor prognosis and PI3K-Akt pathway activation. Our findings indicate that there are some interactions among alterations in the PI3K-Akt pathway and that they could affect prognosis. We characterized p95HER2 expression in GC for the first time. This result supports the use of p95HER2 expression as a biomarker in a future clinical trial of Tmab for GC.
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