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Hum Pathol. 2016 Jul;53:25-34. doi: 10.1016/j.humpath.2016.02.007. Epub 2016 Mar 4.

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

Author information

1
Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
2
Department of Pathology and Institute of Oncology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350004, China.
3
Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China; Department of Pathology, Wuhan Central Hospital, Wuhan 430014, China.
4
Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
5
Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China.
6
Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
7
Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
8
Department of Pathology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China.
9
Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China. Electronic address: chunkuishao2011@163.com.

Abstract

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.

KEYWORDS:

EBVaGC; JAK2; PD-L1; PD-L2; PIK3CA

PMID:
26980034
DOI:
10.1016/j.humpath.2016.02.007
[Indexed for MEDLINE]

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