Prognostic factors in Epstein-Barr virus-associated stage I-III gastric carcinoma: Implications for a unique type of carcinogenesis

Huang,Shih-Chiang; Ng,Kwai-Fong; Chen,Kuang-Hua; Hsu,Jun‑Te; Liu,Keng-Hao; Yeh,Ta-Sen; Chen,Tse-Ching

doi:10.3892/or.2014.3234

Prognostic factors in Epstein-Barr virus-associated stage I-III gastric carcinoma: Implications for a unique type of carcinogenesis

Authors:
- Shih-Chiang Huang
- Kwai-Fong Ng
- Kuang-Hua Chen
- Jun‑Te Hsu
- Keng-Hao Liu
- Ta-Sen Yeh
- Tse-Ching Chen
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Affiliations: Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Guishan, Taoyuan 333, Taiwan, R.O.C., Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Guishan, Taoyuan 333, Taiwan, R.O.C.
Published online on: June 5, 2014 https://doi.org/10.3892/or.2014.3234
Pages: 530-538

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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.

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