Quintanilla-Martínez L, Lome-Maldonado C, Ott G, Gschwendtner A, Gredler E, Reyes E, Angeles-Angeles A, Fend F
Department of Pathology, Instituto Nacional de la Nutrición, México City.
Blood. 1997 Jan 15;89(2):644-51.
Recent studies in Western European populations have shown that peripheral T-cell non-Hodgkin's lymphomas (T-NHLs) are associated with Epstein-Barr virus (EBV) in a higher percentage than sporadic B-cell NHL (B-NHLs), and that the frequency of EBV-positivity might be influenced by the primary site of the tumor. Because of the geographic differences in EBV expression in Burkitt's lymphoma (BL) and Hodgkin's disease (HD), and the lack of studies of sporadic NHL from developing countries, we decided to survey the presence of EBV in a series of primary intestinal lymphomas from patients in Mexico and in Western Europe, and to analyze whether EBV status is influenced by tumor phenotype, and geographic or ethnic determinants. Paraffin-embedded tissue from 43 primary intestinal NHLs (19 cases from Mexico and 24 from Western Europe) were examined, including 17 high grade B-NHLs, 9 low grade B-NHLs, and 17 T-NHLs; 6 of which were enteropathy associated T-cell lymphomas. The distribution of histologic subtypes was similar in both groups. The presence of EBV was investigated with a combined approach using a nested polymerase chain reaction technique as well as immunohistochemistry for latent membrane protein-1 and in situ hybridization for EBV early RNA transcripts (EBER 1/2) RNAs. The median age of the Mexican patients was significantly lower than the median age of the European patients (32 v 62 years). This difference was most pronounced in patients with T-cell lymphoma (24 v 63 years). EBER-positive tumor cells were detected in 13 of the 43 (30%) cases of primary intestinal lymphoma, including 5 of 26 sporadic B-NHL (3 high grade and 2 low grade), and 8 of 17 T-NHL, all of which were classified as pleomorphic, medium and large cell. The rates of EBV-positivity were markedly different for European and Mexican cases. Whereas 7 of 7 (100%) T-NHL and 5 of 12 (42%) sporadic B-NHL of Mexican origin were EBER-positive, only 1 of 10 T-NHL and 0 of 14 sporadic B-NHL from Europe showed EBER expression in tumor cells. Latent membrane protein was positive in only 2 of 43 cases, 1 of which was an EBER-negative high grade B-NHL from Mexico that showed intact total mRNA in control hybridization. CD30 expression was found in 4 of 8 EBV-positive T-NHL and in none of the EBV-positive B-NHL. In contrast to European cases, intestinal NHLs from Mexico show a very high frequency of EBV-positivity, which is not limited to T-NHL, but includes a significant proportion of B-NHL. This study strongly suggests that similar to HD and probably BL, there are important epidemiologic differences in EBV association in intestinal T-cell NHL between European and Mexican populations. These differences might be the result of environmental factors, for example, earlier contact with childhood viruses on intestinal lymphomagenesis.
西欧人群的近期研究表明，外周T细胞非霍奇金淋巴瘤（T-NHL）与爱泼斯坦-巴尔病毒（EBV）的关联比例高于散发性B细胞非霍奇金淋巴瘤（B-NHL），且EBV阳性频率可能受肿瘤原发部位影响。鉴于伯基特淋巴瘤（BL）和霍奇金病（HD）中EBV表达存在地理差异，且缺乏对发展中国家散发性非霍奇金淋巴瘤的研究，我们决定调查墨西哥和西欧患者一系列原发性肠道淋巴瘤中EBV的存在情况，并分析EBV状态是否受肿瘤表型、地理或种族因素影响。对43例原发性肠道非霍奇金淋巴瘤（19例来自墨西哥，24例来自西欧）的石蜡包埋组织进行了检查，包括17例高级别B-NHL、9例低级别B-NHL和17例T-NHL；其中6例为肠病相关T细胞淋巴瘤。两组组织学亚型分布相似。采用巢式聚合酶链反应技术结合免疫组织化学检测潜伏膜蛋白-1以及原位杂交检测EBV早期RNA转录本（EBER 1/2）RNA的联合方法来研究EBV的存在情况。墨西哥患者的中位年龄显著低于欧洲患者（32岁对62岁）。这种差异在T细胞淋巴瘤患者中最为明显（24岁对63岁）。在43例原发性肠道淋巴瘤病例中的13例（30%）检测到EBER阳性肿瘤细胞，包括26例散发性B-NHL中的5例（3例高级别和2例低级别）以及17例T-NHL中的8例，所有这些均被分类为多形性、中大型细胞。欧洲和墨西哥病例的EBV阳性率明显不同。墨西哥起源的7例T-NHL中的7例（100%）和1例12例散发性B-NHL中的5例（42%）EBER阳性，而来自欧洲的10例T-NHL中仅1例和14例散发性B-NHL中0例在肿瘤细胞中显示EBER表达。潜伏膜蛋白仅在43例中的2例呈阳性，其中1例是来自墨西哥的EBER阴性高级别B-NHL，在对照杂交中显示完整的总mRNA。8例EBV阳性T-NHL中有4例发现CD30表达，而EBV阳性B-NHL中均未发现。与欧洲病例相反，来自墨西哥的肠道非霍奇金淋巴瘤显示出非常高的EBV阳性频率，这不仅限于T-NHL，还包括相当比例的B-NHL。这项研究强烈表明，与HD可能还有BL相似，欧洲和墨西哥人群在肠道T细胞非霍奇金淋巴瘤中EBV关联方面存在重要的流行病学差异。这些差异可能是环境因素的结果，例如，儿童期较早接触病毒对肠道淋巴瘤发生的影响。
