Epstein-Barr virus-related gastric adenocarcinoma: An early secondary cancer post hemopoietic stem cell transplantation
Epstein-Barr virus-related gastric adenocarcinoma: An early secondary cancer post hemopoietic stem cell transplantation
复制标题
DOI：
10.1053/j.gastro.2005.10.011
复制
发表时间：
2005-12-01
期刊：
影响因子：
29.4
通讯作者：
Kwong, YL
中科院分区：
文献类型：
--
作者：
Au, WY;Pang, A;Kwong, YL
背景与目的：EB病毒(Epstein-Barr Virus，EBV)感染与某些胃癌有关。方法：我们研究了一例56岁男性骨髓瘤非清髓性造血干细胞移植后发生的早发性胃腺癌。结果：胃腺癌发生前有严重的移植物抗宿主病(GVHD)，需要强烈的免疫抑制，从而导致EBV感染的强烈再激活。在造血干细胞移植后100天、130天和150天进行三次连续的胃活检检查，分别显示胃炎、不典型增生和腺癌。没有幽门螺杆菌感染的证据。循环EBV定量聚合酶链式反应显示，EBV DNA在胃炎时达到高峰，随后逐渐下降，GVHD得到充分控制，免疫抑制逐渐减弱。EBV编码的早期小RNA的原位杂交显示，在胃炎标本中没有EBV，但在不典型增生和癌组织中存在EBV。仅在癌组织中观察到E-钙粘蛋白启动子的异常甲基化，表明EB病毒感染先于E-钙粘蛋白甲基化。结论：移植物抗宿主病引起的粘膜损伤、免疫抑制和EBV激活共同导致了胃细胞的EBV感染和癌变，提示该病例是真正的EBV相关的移植后机会性恶性肿瘤。一个有趣的命题是，这个病例也可能反映了在免疫功能正常的患者中发生EBV相关胃癌的紧凑时间线。
Background & Aims: Epstein-Barr virus (EBV) infection has been associated with some cases of gastric cancer. Methods: We studied a case of early onset gastric adenocarcinoma after nonmyeloablative hematopoietic stem cell transplantation for myeloma in a 56-year-old man. Results: The development of gastric adenocarcinoma was preceded by severe graft-versus-host disease (GVHD) necessitating strong immunosuppression, which resulted in an intense reactivation of EBV infection. Three sequential gastric biopsy examinations performed at 100, 130, and 150 days after hematopoietic stem cell transplantation showed gastritis, dysplasia, and adenocarcinoma, respectively. There was no evidence of Helicobacter pylori infection. Quantitative polymerase chain reaction for circulating EBV showed a surge of EBV DNA peaking at the time of gastritis, followed by a gradual decrease afterward with adequate control of GVHD and tailing of immunosuppression. In situ hybridization for EBV-encoded early small RNA showed absence of EBV in the gastritis specimen, but the presence of EBV in the dysplastic and carcinoma specimens. Aberrant promoter methylation of E-cadherin was observed only in the carcinoma specimens, showing that infection with EBV preceded E-cadherin methylation. Conclusions: Mucosal damage caused by GVHD, immunosuppression, and EBV reactivation combined to lead to EBV infection of the gastric cells and initiation of carcinogenesis, suggesting this case to be a genuine EBV-related opportunistic malignancy post-transplantation. An interesting proposition is that this case also might reflect a compacted timeline of events in EBV-related gastric cancers developing in immunocompetent patients.