Preciado M V, De Matteo E, Diez B, Menárguez J, Grinstein S
Laboratory of Virology, Ricardo Gutierrez Children's Hospital, Buenos Aires, Argentina.
Blood. 1995 Nov 15;86(10):3922-9.
Epstein-Barr virus (EBV) has been implicated in the etiology of a large number of malignancies. Most recently several studies have linked EBV to Hodgkin's disease. In this report, formalin-fixed, paraffin-embedded tissues were collected retrospectively from 41 children with Hodgkin's disease treated at our hospital. Lymph node biopsies were examined for the presence of two virus-encoded latent proteins: latent membrane protein (LMP) and Epstein-Barr nuclear antigen-2 (EBNA-2), in Reed-Sternberg (RS) and Hodgkin (H) cells, by peroxidase immunolabeling. Nonisotopic Epstein-Barr encoded RNAs (EBERs) in situ hybridization was also performed and positive labeling in malignant cells was detected. Twenty specimens were EBER+/LMP+, 2 were EBER+/LMP-, and 19 were EBER-/LMP-. However, none of the 41 cases expressed EBNA-2. Twenty-two of 41 (54%) cases were EBV positive including 2 of 6 with lymphocyte predominance, 19 of 25 with mixed cellularity, 0 of 9 with nodular sclerosis, and 1 of 1 with lymphocyte depletion. In the age range of 2 to 6 years, 14 of 17 (82%) samples were EBV-positive, whereas only 8 of 24 (33%) samples from the age range of 7 to 15 years contained EBV. (P = .004), a two-tailed Fisher's test). In 17 samples, polymerase chain reaction amplification was performed using strain specific primers for exon sequences of the EBNA-3C gene of EBV. From 12 positive samples, 8 contained EBV-A and 4 EBV-B. These results support the hypothesis that EBV contributes to the pathogenesis of pediatric Hodgkin's disease, particularly in mixed cellularity Hodgkin's disease and in the younger group.
爱泼斯坦-巴尔病毒(EBV)与多种恶性肿瘤的病因有关。最近有几项研究将EBV与霍奇金病联系起来。在本报告中,我们回顾性收集了我院治疗的41例霍奇金病患儿经福尔马林固定、石蜡包埋的组织。通过过氧化物酶免疫标记法,检测了里德-斯腾伯格(RS)细胞和霍奇金(H)细胞中两种病毒编码的潜伏蛋白:潜伏膜蛋白(LMP)和爱泼斯坦-巴尔核抗原2(EBNA-2)的存在情况。还进行了非同位素爱泼斯坦-巴尔编码RNA(EBERs)原位杂交,并在恶性细胞中检测到阳性标记。20个标本为EBER+/LMP+,2个为EBER+/LMP-,19个为EBER-/LMP-。然而,41例病例中无一例表达EBNA-2。41例(54%)病例中有22例EBV阳性,其中淋巴细胞为主型6例中有2例,混合细胞型25例中有19例,结节硬化型9例中0例,淋巴细胞消减型1例中有1例。在2至6岁年龄组中,17例样本中有14例(82%)EBV阳性,而7至15岁年龄组的24例样本中只有8例(33%)含有EBV。(P = 0.004,双侧费舍尔检验)。对17个样本进行了聚合酶链反应扩增,使用针对EBV的EBNA-3C基因外显子序列的菌株特异性引物。在12个阳性样本中,8个含有EBV-A,4个含有EBV-B。这些结果支持了EBV参与儿童霍奇金病发病机制的假说,特别是在混合细胞型霍奇金病和较年轻组中。