TY - JOUR T1 - Exon 9 Mutation of <em>PIK3CA</em> Associated With Poor Survival in Patients With Epstein-Barr Virus-associated Gastric Cancer JF - Anticancer Research JO - Anticancer Res SP - 2145 LP - 2154 DO - 10.21873/anticanres.13328 VL - 39 IS - 4 AU - AN NA SEO AU - BYUNG WOOG KANG AU - HAN IK BAE AU - OH KYOUNG KWON AU - KI BUM PARK AU - SEUNG SOO LEE AU - HO YOUNG CHUNG AU - WANSIK YU AU - SEONG WOO JEON AU - HYOJEUNG KANG AU - JONG GWANG KIM Y1 - 2019/04/01 UR - http://ar.iiarjournals.org/content/39/4/2145.abstract N2 - Background: Epstein-Barr virus (EBV)-associated gastric cancer (GC) is known to harbor a significant enrichment of of phosphatidylinositol 4, 5-biphosphate 3- kinase catalytic subunit alpha isoform (PIK3CA). Therefore, this study investigated the clinical relevance and prognostic role of PIK3CA mutations in patients with EBV-GC. Materials and Methods: After reviewing 1,318 consecutive cases of surgically resected GC, 120 patients were identified as EBV-positive using EBV-encoded RNA in situ hybridization. PIK3CA mutations were identified in formalin-fixed and paraffin-embedded surgical specimens from 112 patients with EBV-GC with available tumor tissue samples. Real-time polymerase chain reaction was used to evaluate hot-spot mutations of exons 1, 4, 7, 9, and 20 of PIK3CA. Results: Among the 112 patients, the frequency of PIK3CA mutations was 25.0% (n=28), and among the 28 patients harboring a PIK3CA mutation, most mutations were identified in exon 9 (n=21, 18.8%). The presence of PIK3CA mutation was also correlated with a higher T category (p&lt;0.001) and N category (p&lt;0.001), as well as the presence of perinueral invasion (p&lt;0.001) and venous invasion (p&lt;0.001). In a univariate analysis, PIK3CA mutation showed no association with overall survival (OS) (p=0.184) or disease-free survival (DFS) (p=0.150). Patients harboring exon 9 PIK3CA mutations exhibited a significantly shorter OS (p=0.023) and DFS (p=0.013) than the patients lacking an exon 9 PIK3CA mutation, yet without statistical significance in the multivariate analysis. Notably, exon 9 E542K mutation of PIK3CA was associated with the worst DFS (p=0.011). Conclusion: The current data show that PIK3CA mutations appear to play an important role in carcinogenesis and tumor aggressiveness in EBV-GC, and also support the concept that exon 9 mutation of PIK3CA is a prognostic indicator for predicting patient outcomes and a rationale for therapeutic targeting in EBV-GC. ER -