Expression and prognostic roles of PIK3CA, JAK2, PD-L1, and PD-L2 in Epstein-Barr virus-associated gastric carcinoma

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• 作者：Min Dong ; MD^a ; ¹ ; Hai-yan Wang ; MD^b ; ¹ ; Xiao-xiao Zhao ; MD^c ; ^d ; Jian-ning Chen ; MD^c ; Yi-wang Zhang ; PhD^c ; Yan Huang ; MD^e ; Ling Xue ; PhD^f ; Hai-gang Li ; PhD^g ; Hong Du ; MD^h ; Xiang-yuan Wu ; MD^a ; Chun-kui Shao ; PhD ; MD^c ; ^{chunkuishao2011@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：EBVaGC ; PIK3CA ; JAK2 ; PD-L1 ; PD-L2
• 刊名：Human Pathology
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：53
• 期：Complete
• 页码：25-34
• 全文大小：1523 K

文摘

As a special subtype of gastric carcinoma, Epstein-Barr virus (EBV)–associated gastric carcinoma (EBVaGC) has distinct clinicopathological features. The Cancer Genome Atlas Research Network revealed that EBVaGC also has distinct molecular features: PIK3CA mutations, DNA hypermethylation, and JAK2, PD-L1, and PD-L2 amplification. Here, we evaluated PIK3CA, JAK2, PD-L1, and PD-L2 expression in 59 EBVaGC and 796 EBV-negative gastric carcinoma (EBVnGC) cases using immunohistochemistry and found that PIK3CA, JAK2, PD-L1, and PD-L2 were highly expressed in 75.9% and 48.8% (P < .001), 81.8% and 71.1% (P = .091), 92.5% and 84.8% (P = .132), and 98.1% and 89.7% (P = .049) of the EBVaGC and EBVnGC cases, respectively. However, the expression of PIK3CA, JAK2, PD-L1, or PD-L2 was not significantly associated with clinicopathological features or patient outcomes in EBVaGC. In contrast, in EBVnGC, high PIK3CA expression was significantly associated with indolent clinicopathological features and independently predicted better 5-year overall survival (57.8% versus 33.4%, P < .001). Our study indicated that the protein expression of the 4 characteristic molecules of EBVaGC was basically consistent with their genetic alterations, making them potential characteristic protein biomarkers and therapeutic targets of EBVaGC. The favorable impact of PIK3CA overexpression on survival found in this study gives us new insight into the clinical significance of PIK3CA in EBVnGC.