Volume 129, Issue 6, Pages 2058-2063 (December 2005) Epstein–Barr Virus–Related Gastric Adenocarcinoma: An Early Secondary Cancer Post Hemopoietic Stem Cell Transplantation  Wing–Yan Au, Annie Pang, Eunice C. Chan, Kent–Man Chu, Tony W.H. Shek, Yok–Lam Kwong  Gastroenterology  Volume 129, Issue 6, Pages 2058-2063 (December 2005) DOI: 10.1053/j.gastro.2005.10.011 Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 1 Histopathologic features of a case of EBV-positive gastric cancer post-HSCT. (A) Gastric biopsy specimen on day 100 showing acute gastritis with marked edema in the lamina propria, with predominantly acute and some chronic inflammatory cells. (B) Gastric biopsy specimen on day 130 showing severe epithelial dysplasia, with cytologically and architecturally abnormal cells. (C) Gastrectomy specimen showing an invasive adenocarcinoma with fused neoplastic glands. (D) ISH for EBER showing absence of staining in the gastritis (day 100) specimen. Positive control of ISH for U6, a small nuclear RNA, was positive, showing integrity of RNA (data not shown). Some background staining was seen toward the base of the biopsy specimen. (E) Strong nuclear staining for EBER in the dysplastic (day 100) gastric cells. Background lymphocytes were negative. (F) Strong nuclear staining for EBER in the gastric carcinoma cells. The background lymphocytes were negative. (G) Dual-color fluorescence ISH analysis of the tumor tissue. All analyzable cells (arrows) showed a single X (orange) and a single Y (green) signal, indicating that the cancer cells were recipient in origin. Gastroenterology 2005 129, 2058-2063DOI: (10.1053/j.gastro.2005.10.011) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 2 Quantification of circulating EBV-DNA level in a case of EBV-positive gastric cancer post-HSCT. An increase in EBV-DNA level occurred shortly after HSCT. Further increases ensued with the onset of GVHD and immunosuppression, peaking at the time of detection of gastritis. However, with adequate control of GVHD leading to a decrease in immunosuppression, the EBV-DNA level started to decrease. Cessation of immunosuppression and complete resection of the gastric cancer led to undetectable levels of EBV DNA. Gastroenterology 2005 129, 2058-2063DOI: (10.1053/j.gastro.2005.10.011) Copyright © 2005 American Gastroenterological Association Terms and Conditions

Figure 3 MSP for E-cadherin. The gastritis (gast) specimen did not give any PCR product. In the gastric specimen showing dysplasia (dys), amplification was positive for the unmethylated (U) E-cadherin gene, but negative for the methylated (M) gene. However, in the gastric cancer biopsy specimen (CA1) and the gastrectomy specimen (CA2), E-cadherin methylation was present. P, positive control with methylated DNA showing positive amplification in the M but not U reactions; N, normal control DNA showing positive amplification in the U but not M reactions; B, reagent blank; MW, molecular weight markers. Gastroenterology 2005 129, 2058-2063DOI: (10.1053/j.gastro.2005.10.011) Copyright © 2005 American Gastroenterological Association Terms and Conditions