title: Prognostic factors in Epstein-Barr virus-associated stage I-III gastric carcinoma: implications for a unique type of carcinogenesis.
abstract: Epstein-Barr virus-associated gastric carcinoma (EBVaGC) has distinct clinicopathological features. However, the prognostic factors remain unclear, particularly in UICC/AJCC stage I-III cancer. We retrospectively enrolled 1,020 patients with stage I-III gastric cancer that received radical gastrectomy with lymphadenectomy. Formalin-fixed, paraffin‑embedded surgical specimens were retrieved to construct tissue microarrays. EBV positivity was identified by in situ hybridization with EBV-encoded small RNA, and the histological classification was reviewed. Fifty-two cases of EBVaGC were identified, exhibiting a male predominance (p=0.003), a higher prevalence in stump cancer (p<0.001), and poorly differentiated carcinoma (p=0.010) compared with the controls. The survival analysis revealed no difference in survival between the EBVaGC cases and the EBV-negative cases (p=0.977). The multivariate analysis showed that EBVaGC cases with a tumor size >5 cm, non-lymphoepithelioma-like carcinoma (LELC), or a lymph node ratio >0.15 had a worse overall survival (hazard ratio 2.884, 12.178 and 19.352; p=0.027, 0.005 and <0.0001, respectively). The depth of tumor invasion and the number of lymph node metastases did not reach statistical significance (p=0.834 and 0.833, respectively). These prognostic factors, tumor size, LELC classification and lymph node ratio, may reflect a unique type of carcinogenesis of EBVaGC and may be considered when selecting high-risk patients for adjuvant treatment.
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Guishan, Taoyuan 333, Taiwan, R.O.C.
authors.forename: Shih-Chiang
authors.initials: SC
authors.lastname: Huang
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Guishan, Taoyuan 333, Taiwan, R.O.C.
authors.forename: Kwai-Fong
authors.initials: KF
authors.lastname: Ng
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Guishan, Taoyuan 333, Taiwan, R.O.C.
authors.forename: Kuang-Hua
authors.initials: KH
authors.lastname: Chen
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Guishan, Taoyuan 333, Taiwan, R.O.C.
authors.forename: Jun-Te
authors.initials: JT
authors.lastname: Hsu
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Guishan, Taoyuan 333, Taiwan, R.O.C.
authors.forename: Keng-Hao
authors.initials: KH
authors.lastname: Liu
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Guishan, Taoyuan 333, Taiwan, R.O.C.
authors.forename: Ta-Sen
authors.initials: TS
authors.lastname: Yeh
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Guishan, Taoyuan 333, Taiwan, R.O.C.
authors.forename: Tse-Ching
authors.initials: TC
authors.lastname: Chen
mesh_terms: D000368:Aged; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis* / Q000601:surgery / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D011379:Prognosis; D058727:RNA, Small Untranslated / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000473:pathology* / Q000821:virology; D016019:Survival Analysis
chemical_list: D058727:RNA, Small Untranslated; D012367:RNA, Viral