Herbst H, Dallenbach F, Hummel M, Niedobitek G, Finn T, Young L S, Rowe M, Müller-Lantzsch N, Stein H
Institute of Pathology, Klinikum Steglitz, Free University of Berlin, Germany.
Blood. 1991 Nov 15;78(10):2666-73.
Epstein-Barr virus (EBV)-specific DNA sequences were detected by polymerase chain reaction analysis in 15 of 47 (32%) DNA extracts prepared from CD30-positive (Ki-1 antigen-positive) anaplastic large cell (ALC) lymphomas. EBV-encoded RNA (EBER) transcripts could be detected by in situ hybridization in the tumor cells of 9 of 11 EBV DNA-positive cases. Twenty-eight cases were examined by immunohistology on cryostat sections for the presence of the EBV-encoded latent membrane protein (LMP), the nuclear antigen 2 (EBNA2), the BZLF1 transactivator protein, and the late viral glycoprotein gp350/250. A distinct LMP-specific membrane and cytoplasmic staining was detected exclusively in lymphoma cells of five cases (18%); two of these cases additionally expressed EBNA2. BZLF1 protein and gp350/250 immunoreactivity was absent in all instances. All LMP-positive cases contained EBV DNA and EBER sequences. The pattern of EBV latent protein expression in ALC lymphomas showed heterogeneity with respect to EBNA2 expression: LMP-positive/EBNA2-negative cases displayed a pattern previously described for undifferentiated nasopharyngeal carcinomas and Hodgkin's disease, whereas LMP-positive and EBNA2-positive cases showed parallels to lymphoblastoid cell lines. Because the LMP gene has transforming potential, our findings support the concept of a pathoetiologic role for EBV in a proportion of CD30-positive ALC lymphomas.
通过聚合酶链反应分析,在从CD30阳性(Ki-1抗原阳性)间变性大细胞(ALC)淋巴瘤制备的47份DNA提取物中的15份(32%)中检测到爱泼斯坦-巴尔病毒(EBV)特异性DNA序列。在11例EBV DNA阳性病例中的9例肿瘤细胞中,通过原位杂交可检测到EBV编码的RNA(EBER)转录本。对28例病例的低温切片进行免疫组织化学检查,以检测EBV编码的潜伏膜蛋白(LMP)、核抗原2(EBNA2)、BZLF1反式激活蛋白和晚期病毒糖蛋白gp350/250的存在情况。仅在5例(18%)病例的淋巴瘤细胞中检测到明显的LMP特异性膜和细胞质染色;其中2例还表达EBNA2。所有病例均未检测到BZLF1蛋白和gp350/250免疫反应性。所有LMP阳性病例均含有EBV DNA和EBER序列。ALC淋巴瘤中EBV潜伏蛋白表达模式在EBNA2表达方面表现出异质性:LMP阳性/EBNA2阴性病例呈现出先前描述的未分化鼻咽癌和霍奇金病的模式,而LMP阳性和EBNA2阳性病例则与淋巴母细胞系相似。由于LMP基因具有转化潜能,我们的研究结果支持EBV在一部分CD30阳性ALC淋巴瘤中具有致病作用的概念。