van Beek Josine, zur Hausen Axel, Klein Kranenbarg Elma, van de Velde Cornelis J H, Middeldorp Jaap M, van den Brule Adriaan J C, Meijer Chris J L M, Bloemena Elisabeth
Department of Pathology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
J Clin Oncol. 2004 Feb 15;22(4):664-70. doi: 10.1200/JCO.2004.08.061.
Epstein-Barr virus (EBV) is detected in a substantial subgroup of gastric adenocarcinomas worldwide. We have previously reported that these EBV-positive gastric carcinomas carry distinct genomic aberrations. In the present study, we analyzed a large cohort of EBV-positive and EBV-negative gastric adenocarcinomas for their clinicopathologic features to determine whether they constitute a different clinical entity.
Using a validated polymerase chain reaction/enzyme immunoassay-based prescreening method in combination with EBER1/2-RNA in situ hybridization, EBV was detected in the tumor cells of 7.2% (n = 41) of the gastric carcinomas from the Dutch D1D2 trial (N = 566; mean follow-up, 9 years). EBV status was correlated with clinicopathologic features collected for the Dutch D1D2 trial.
EBV-positive gastric carcinomas occurred significantly more frequently in males (P <.0001) and in younger patients (P =.012). Most were of the intestinal type according to the Laurén classification (P =.047) or tubular according to the WHO classification (P =.006) and located in the proximal part of the stomach (P <.0001). A significantly lower tumor-node-metastasis system-stage (P =.026) was observed in the patients with EBV-carrying carcinomas, which was solely explained by less lymph node (LN) involvement (P =.034) in these cases. In addition, a better prognosis, as reflected by a longer disease-free period (P =.04) and a significant better cancer-related survival (P =.02), was observed for these patients, which could be explained by less LN involvement, less residual disease, and younger patient age.
EBV-carrying gastric adenocarcinomas are a distinct entity of carcinomas, characterized not only by unique genomic aberrations, but also by distinct clinicopathologic features associated with significantly better prognosis.
在全球范围内,相当一部分胃腺癌中可检测到爱泼斯坦-巴尔病毒(EBV)。我们之前曾报道,这些EBV阳性胃癌存在独特的基因组畸变。在本研究中,我们分析了一大组EBV阳性和EBV阴性胃腺癌的临床病理特征,以确定它们是否构成不同的临床实体。
采用经过验证的基于聚合酶链反应/酶免疫测定的预筛查方法,并结合EBER1/2-RNA原位杂交,在荷兰D1D2试验(N = 566;平均随访9年)的7.2%(n = 41)胃癌肿瘤细胞中检测到EBV。EBV状态与荷兰D1D2试验收集的临床病理特征相关。
EBV阳性胃癌在男性中发生频率显著更高(P <.0001),且在年轻患者中更常见(P =.012)。根据劳伦分类,大多数为肠型(P =.047),或根据世界卫生组织分类为管状(P =.006),且位于胃近端(P <.0001)。携带EBV的癌患者中观察到肿瘤-淋巴结-转移系统分期显著更低(P =.026),这完全是由于这些病例中淋巴结受累较少(P =.034)。此外,这些患者预后更好,表现为无病生存期更长(P =.04)以及癌症相关生存率显著更高(P =.02),这可以通过淋巴结受累较少、残留疾病较少以及患者年龄较轻来解释。
携带EBV的胃腺癌是一种独特的癌实体,不仅具有独特的基因组畸变,还具有与显著更好预后相关的独特临床病理特征。