Hell K, Lorenzen J, Fischer R, Hansmann M L
Department of Pathology, University of Cologne, Germany.
Lab Invest. 1995 Oct;73(4):492-6.
The bcl-2 oncogene is able to prevent cells from apoptosis. Overexpression of the bcl-2 protein seems to be important for the pathogenesis of follicular center cell lymphomas, in which both protein and mRNA usually show high levels. In addition, the expression of the Epstein-Barr virus-encoded late membrane protein up-regulates the bcl-2 protein in cell lines. The aim of the current study was to investigate the expression of the bcl-2 oncogene in Hodgkin's disease both at the protein and mRNA level in correlation with the expression of the late membrane protein.
Thirteen cases of all histologic types of Hodgkin's disease, six cases of chronic nonspecific lymphadenitis, three tonsils with follicular hyperplasia, seven cases of follicular small cleaved cell lymphoma, and six cases of follicular large cell lymphoma, were analyzed. We designed a novel digoxigenin-labeled oligonucleotide probe complementary to bcl-2 mRNA for nonisotopic in situ hybridization. Bcl-2 oncoprotein and late membrane protein expression were determined by immunohistochemistry. The presence of the 14;18 translocation was analyzed by PCR for the major breakpoint region.
The main finding was that, irrespective of subtype, the vast majority of Hodgkin cells express abundant bcl-2 mRNA. Oncoprotein expression, however, varied from case to case, with the highest prevalence in the nodular sclerosing subtype, and showed no strict correlation with the late membrane protein. In our case, no 14;18 translocation could be found in Hodgkin's disease.
Hodgkin cells in all types of Hodgkin's disease demonstrated high levels of bcl-2 mRNA, while the bcl-2 protein expression was inhomogenous. In nodular lymphocyte predominant type, the bcl-2 mRNA and protein pattern is comparable to germinal center cells. This finding is a further argument for the germinal center cell origin of this type of Hodgkin's disease.
bcl-2癌基因能够阻止细胞凋亡。bcl-2蛋白的过度表达似乎对滤泡中心细胞淋巴瘤的发病机制很重要，在这类淋巴瘤中，蛋白和mRNA通常都呈现高水平。此外，爱泼斯坦-巴尔病毒编码的晚期膜蛋白的表达可上调细胞系中的bcl-2蛋白。本研究的目的是在蛋白和mRNA水平上研究bcl-2癌基因在霍奇金病中的表达，并与晚期膜蛋白的表达相关联。
分析了13例所有组织学类型的霍奇金病、6例慢性非特异性淋巴结炎、3例伴有滤泡增生的扁桃体、7例滤泡性小裂细胞淋巴瘤和6例滤泡性大细胞淋巴瘤。我们设计了一种与bcl-2 mRNA互补的新型地高辛标记寡核苷酸探针，用于非同位素原位杂交。通过免疫组织化学测定bcl-2癌蛋白和晚期膜蛋白的表达。通过PCR分析主要断裂点区域来检测14;18易位的存在。
主要发现是，无论亚型如何，绝大多数霍奇金细胞都表达丰富的bcl-2 mRNA。然而，癌蛋白的表达因病例而异，在结节硬化亚型中患病率最高，并且与晚期膜蛋白没有严格的相关性。在我们的病例中，未在霍奇金病中发现14;18易位。
所有类型霍奇金病中的霍奇金细胞均显示高水平的bcl-2 mRNA，而bcl-2蛋白表达不均匀。在结节性淋巴细胞为主型中，bcl-2 mRNA和蛋白模式与生发中心细胞相当。这一发现进一步支持了这类霍奇金病起源于生发中心细胞的观点。
