爱泼斯坦-巴尔病毒与艾滋病青年患者平滑肌肉瘤的关联。

Association of Epstein-Barr virus with leiomyosarcomas in young people with AIDS.

作者信息

McClain K L, Leach C T, Jenson H B, Joshi V V, Pollock B H, Parmley R T, DiCarlo F J, Chadwick E G, Murphy S B

机构信息

Department of Pediatrics, Baylor College of Medicine, Houston, TX.

出版信息

N Engl J Med. 1995 Jan 5;332(1):12-8. doi: 10.1056/NEJM199501053320103.

DOI:10.1056/NEJM199501053320103

PMID:7990860

Abstract

BACKGROUND

Children with the acquired immunodeficiency syndrome (AIDS) have an unusually high incidence of smooth-muscle tumors (leiomyomas and leiomyosarcomas) in addition to malignant lymphomas. We tested the hypothesis that the smooth-muscle tumors in these children are associated with the Epstein-Barr virus (EBV).

METHODS

Tissue specimens of five leiomyosarcomas and two leiomyomas from six children with AIDS were studied for evidence of the human immunodeficiency virus (HIV) and EBV by in situ hybridization and quantitative polymerase chain reaction (PCR). Comparison specimens included samples of leiomyosarcoma and leiomyoma from HIV-negative children. EBV clonality of leiomyosarcomas was determined by Southern blot analysis with oligonucleotide probes for EBV terminal-repeat fragments. Tumor specimens were tested by immunoperoxidase staining for infiltration by B lymphocytes and expression of the EBV receptor. Serologic testing for EBV was performed.

RESULTS

In situ hybridization showed EBV genomes in all muscle cells of the five leiomyosarcomas and the two leiomyomas from the six HIV-infected children. Quantitative PCR demonstrated strikingly high levels of EBV in tumor tissue, with as many as 4.3 genome copies per cell. Two colonic leiomyosarcomas obtained from different sites at different times from one patient contained different episomal EBV clones, signifying the presence of distinct monoclonal EBV-related tumors. We found biclonal EBV infection in the leiomyosarcoma of another patient. No EBV was detected in normal muscle or tumor specimens from HIV-negative patients. Immunostaining for the EBV receptor was strongly positive in six of the seven leiomyomas and leiomyosarcomas from the patients with AIDS.

CONCLUSIONS

EBV can infect smooth-muscle cells, at least in patients with AIDS, and it may contribute to the pathogenesis of leiomyomas and leiomyosarcomas in children with AIDS. EBV seems to play no part in smooth-muscle tumors in HIV-negative children.

摘要

背景

获得性免疫缺陷综合征（艾滋病）患儿除恶性淋巴瘤外，平滑肌肿瘤（平滑肌瘤和平滑肌肉瘤）的发病率异常高。我们检验了这样一个假设，即这些患儿的平滑肌肿瘤与爱泼斯坦-巴尔病毒（EBV）有关。

方法

通过原位杂交和定量聚合酶链反应（PCR），对6名艾滋病患儿的5例平滑肌肉瘤和2例平滑肌瘤的组织标本进行了人类免疫缺陷病毒（HIV）和EBV检测。对照标本包括来自HIV阴性儿童的平滑肌肉瘤和平滑肌瘤样本。用针对EBV末端重复片段的寡核苷酸探针进行Southern印迹分析，以确定平滑肌肉瘤的EBV克隆性。通过免疫过氧化物酶染色检测肿瘤标本中B淋巴细胞的浸润情况和EBV受体的表达。对EBV进行了血清学检测。

结果

原位杂交显示，6名HIV感染患儿的5例平滑肌肉瘤和2例平滑肌瘤的所有肌肉细胞中均有EBV基因组。定量PCR显示肿瘤组织中EBV水平极高，每个细胞多达4.3个基因组拷贝。从一名患者不同时间不同部位获取的2例结肠平滑肌肉瘤含有不同的游离型EBV克隆，表明存在不同的单克隆EBV相关肿瘤。我们在另一名患者的平滑肌肉瘤中发现了双克隆EBV感染。在HIV阴性患者的正常肌肉或肿瘤标本中未检测到EBV。艾滋病患者的7例平滑肌瘤和平滑肌肉瘤中有6例的EBV受体免疫染色呈强阳性。