Abstract 485: Exon 9 mutation of PIK3CA associated with poor survival in patients with Epstein-Barr virus-associated gastric cancer
Authors: Baek Dongwon , Kim Jong Gwang , Baek Jin Ho , Kang Byung Woog , Lee Soo Jung , Chae Yee Soo , Cho Hee Jeong 
Published: August 2019

Abstract
PIK3CA would seem to play an important role in the prognosis of gastric cancer (GC), very few studies have reported on the clinical implications and prognostic effects of these mutations in patients with Epstein-Barr virus-associated gastric cancer (EBVaGC). This study attempted to identify the prognostic significance of PIK3CA mutations in a large number of EBVaGC patients and the relationship of these mutations to the clinicopathologic parameters associated with prognosis. After reviewing 1318 consecutive cases of surgically resected at our institution between January 2011 and November 2014, 120 patients were identified as EBV-positive using EBV-encoded RNA in situ hybridization. Among the 120 patients, 8 patients were excluded due to insufficient or unavailable material (6 patients) and technical issues (2 patients). The related medical files and pathologic reports were all reviewed to identify the clinical and demographic characteristics. PIK3CA mutations were identified in formalin-fixed and paraffin-embedded surgical specimens from 112 EBVaGC patients with available tumor tissue sample. A real-time polymerase chain reaction was used to evaluate hot-spot mutations of exons 1, 4, 7, 9, and 20 of PIK3CA. The frequency of PIK3CA mutations was 25.0% (n=28), and among the 28 patients harboring a PIK3CA mutation, most of the mutations were identified in exon 9 (n=21, 75%). 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). The patients harboring exon 9 PIK3CA mutations did exhibit 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, the exon 9 E542K mutation of PIK3CA was associated with the worst DFS (P=0.011). Plus, the PIK3CA-mutant tumors were not related to such immune-related factors as intratumoral (iTu) tumor-infiltrating lymphocytes (TILs), stromal (str) TILs, iTu-PD-L1, and str-PD-L1 (all P &gt; 0.05). The PIK3CAmutations harbored in exon 9 were also strongly related to clinicopathologic parameters associated with an unfavorable prognosis. Although the exon 9 PIK3CA mutations were not identified as an independently robust prognostic factor, they could play an important role in carcinogenesis and tumor aggressiveness in EBVaGC. Consequently, these findings support the theory that exon 9 PIK3CA mutations can be a prognostic indicator for predicting patients’ outcomes and a rationale for therapeutic targeting in EBVaGC.
Citation Format: Dongwon Baek, Jong Gwang Kim, Jin Ho Baek, Byung Woog Kang, Soo Jung Lee, Yee Soo Chae, Hee Jeong Cho. Exon 9 mutation of PIK3CA associated with poor survival in patients with Epstein-Barr virus-associated gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 485.