Biomarkers of EBV-positive Gastric Cancers: Loss of PTEN Expression is Associated with Poor Prognosis and Nodal Metastasis

Background: Epstein–Barr virus-positive gastric carcinoma (EBVGC) constitutes approximately 10 % of all gastric carcinoma cases. While distinct molecular features have been characterized previously, there have not been studies identifying their clinical utility. The purpose of this study was to investigate the immunohistochemistry (IHC) profile of EBVGC and to evaluate the potential clinicopathologic and prognostic significance of each marker. Methods: Clinicopathologic characteristics of 234 patients (203 males and 31 females) who underwent curative gastrectomy for EBVGCs from 1998 to 2013 at Asan Medical Center, were reviewed, and IHC for ARID1A, PTEN, PD-L1, p53, p16^INK4a, MLH1, and MSH2 were performed on tissue microarrays. These markers along with several tumor characteristics, e.g., lymphovascular invasion and the extent of differentiation, were analyzed for significant associations as well as any prognostic significance by multivariate analysis. Results: In multivariate analysis, PTEN loss was as an independent factor associated with poor prognosis (p = 0.011). Furthermore, PTEN loss was an independent risk factor for nodal metastasis (p = 0.038). No other biomarkers, ARID1A, PD-L1, p53, p16^INK4a, MLH1, or MSH2, demonstrated significant prognostic value. Conclusions: PTEN loss in EBVGC is a poor prognostic factor associated with mortality and nodal metastasis in EBVGCs. Evaluation of PTEN expression may be helpful to determine the most appropriate treatment strategy, especially for endoscopically resected EBVGCs.