title: Biomarkers of EBV-positive Gastric Cancers: Loss of PTEN Expression is Associated with Poor Prognosis and Nodal Metastasis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pathology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Department of Surgery, Ulsan University College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: In-Seob
authors.initials: IS
authors.lastname: Lee
authors.affiliation: Department of Pathology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Republic of Korea. youngspark@amc.seoul.kr.
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Medicine, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Won Jin
authors.initials: WJ
authors.lastname: Ho
authors.affiliation: Department of Pathology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: DaHye
authors.initials: D
authors.lastname: Sohn
authors.affiliation: Department of Gastroenterology, Ulsan University College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Ji-Yong
authors.initials: JY
authors.lastname: Ahn
authors.affiliation: Department of Surgery, Ulsan University College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Jeong-Hwan
authors.initials: JH
authors.lastname: Yook
authors.affiliation: Department of Surgery, Ulsan University College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Byung-Sik
authors.initials: BS
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism* / Q000601:surgery / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D005743:Gastrectomy; D004854:Herpesvirus 4, Human; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1 / Q000378:metabolism; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000601:surgery / Q000821:virology; D015996:Survival Rate; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C112476:ARID1A protein, human; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein