Kneba M, Eick S, Herbst H, Pott C, Bolz I, Dallenbach F, Hiddemann W, Stein H
Department of Internal Medicine, Georg-August-University, Göttingen, Germany.
J Pathol. 1995 Apr;175(4):381-9. doi: 10.1002/path.1711750404.
Lymph node biopsies from 140 cases of Hodgkin's disease (HD) and from 30 non-malignant lesions were screened for the presence of t(14;18) translocations involving the major breakpoint region (mbr) of the bcl-2 gene and the joining region (JH) of the immunoglobulin heavy chain gene, using a polymerase chain reaction (PCR) assay with subsequent nucleotide sequencing of amplified bcl-2/JH junctional regions. Expression of the bcl-2 protein within the Hodgkin and Reed-Sternberg (HRS) cells was investigated in 86 cases of HD by immunohistochemistry on cryostat or paraffin sections. Although bcl-2 expression could be found in a proportion of neoplastic cells in up to one-third of HD cases, the frequency of t(14;18) gene fusions detected by PCR was low. We identified such gene fusions in only 3 out of 140 (2 per cent) HD cases, one biopsy of which presented with four clonally distinct bcl-2/JH sequences. No t(14;18) was found in any of 30 reactive lymph node lesions. All fusion gene sequences were unique regarding the localization of the chromosome 14 and 18 breakpoints and the extranucleotide N-insertions. None of these gene fusions conformed to t(14;18) breakpoint sequences previously characterized in our laboratories. Our findings point to a mere coincidence in some cases of HD lesions and cells carrying a t(14;18) in the same biopsy and argue against a significant role of bcl-2 in the pathogenesis of HD.
对140例霍奇金淋巴瘤（HD）患者以及30例非恶性病变患者的淋巴结活检样本进行筛查，通过聚合酶链反应（PCR）检测并对扩增后的bcl-2/免疫球蛋白重链基因连接区（JH）进行核苷酸测序，以确定是否存在涉及bcl-2基因主要断裂点区域（mbr）和免疫球蛋白重链基因连接区（JH）的t(14;18)易位。采用免疫组织化学方法，在低温恒温器切片或石蜡切片上，对86例HD患者霍奇金和里德-斯腾伯格（HRS）细胞中的bcl-2蛋白表达情况进行研究。虽然在高达三分之一的HD病例中，部分肿瘤细胞可检测到bcl-2表达，但通过PCR检测到的t(14;18)基因融合频率较低。在140例HD病例中，仅3例（2%）检测到此类基因融合，其中1例活检样本呈现出4种克隆性不同的bcl-2/JH序列。30例反应性淋巴结病变中均未发现t(14;18)。所有融合基因序列在14号和18号染色体断点的定位以及额外核苷酸N插入方面均具有独特性。这些基因融合均不符合我们实验室先前鉴定的t(14;18)断点序列。我们的研究结果表明，在某些HD病例中，病变组织和细胞中携带t(14;18)可能只是巧合，这表明bcl-2在HD发病机制中可能不起重要作用。
