Skinnider B F, Horsman D E, Dupuis B, Gascoyne R D
Department of Pathology, British Columbia Cancer Agency, Vancouver General Hospital, Canada.
Hum Pathol. 1999 Jul;30(7):803-8. doi: 10.1016/s0046-8177(99)90141-7.
The bcl-2 gene on chromosome 18 at q21 and the bcl-6 gene on chromosome 3 at q27 are both highly regulated during B-cell differentiation and show an inverse relationship of expression in the normal secondary lymphoid follicle. The objective of this study was to investigate the relationship between bcl-2 and bcl-6 protein expression and the relationship between protein expression and the corresponding chromosomal alterations in malignant lymphomas, including those associated with the germinal center. Expression of bcl-2 and bcl-6 proteins was studied in 55 cases of diffuse large B-cell lymphoma (DLBCL) and 21 cases of follicular lymphoma (FL), and the results correlated with the presence of t(14;18) and 3q27 abnormalities in a subset of 52 cases with cytogenetic analysis. These cases were selected to represent a spectrum of nodal and extranodal lymphomas, including those with and without a t(14;18). It was shown that the neoplastic cells in 71% of DLBCLs and 100% of FLs expressed bcl-6 protein. Expression of bcl-6 was seen more frequently in diffuse large B-cell lymphomas with large noncleaved morphology compared with immunoblastic morphology (82% v 27%, P = .0015), but failed to correlate with 3q27 abnormalities. Thirty-eight percent of cases with 3q27 abnormalities were bcl-6 protein negative, whereas 85% of cases without a 3q27 abnormalities were bcl-6 protein positive. Expression of bcl-2 protein was shown in 51% DLBCLs (nodal v extranodal, 71% v 30%, P = .012). bcl-2 protein was expressed in 89% of FLs with t(14;18), in contrast to 25% of FLs without t(14;18) (P = .016). In DLBCL and FL with t(14;18), the most common pattern of expression was bcl-2+/bcl-6+. In lymphomas without t(14;18), there was not an inverse relationship between bcl-2 and bcl-6 protein expression. In conclusion, these data suggest that mechanisms other than gene rearrangements can deregulate bcl-2 and bcl-6 expression in lymphomas, and there does not appear to be an inverse relationship between these two proteins as seen in the normal germinal center.
位于18号染色体q21的bcl-2基因和位于3号染色体q27的bcl-6基因在B细胞分化过程中均受到高度调控，且在正常次级淋巴滤泡中呈现出表达的负相关关系。本研究的目的是探讨bcl-2和bcl-6蛋白表达之间的关系，以及在恶性淋巴瘤（包括与生发中心相关的淋巴瘤）中蛋白表达与相应染色体改变之间的关系。对55例弥漫性大B细胞淋巴瘤（DLBCL）和21例滤泡性淋巴瘤（FL）进行了bcl-2和bcl-6蛋白表达的研究，并将结果与52例进行细胞遗传学分析的病例子集的t(14;18)和3q27异常情况相关联。选择这些病例以代表一系列淋巴结和结外淋巴瘤，包括有和没有t(14;18)的病例。结果显示，71%的DLBCL和100%的FL中的肿瘤细胞表达bcl-6蛋白。与免疫母细胞形态的弥漫性大B细胞淋巴瘤相比，具有大无裂细胞形态的弥漫性大B细胞淋巴瘤中bcl-6的表达更常见（82%对27%，P = .0015），但与3q27异常无相关性。3q27异常的病例中有38%为bcl-6蛋白阴性，而无3q27异常的病例中有85%为bcl-6蛋白阳性。51%的DLBCL显示bcl-2蛋白表达（淋巴结型对结外型，71%对30%，P = .012）。89%有t(14;18)的FL表达bcl-2蛋白，相比之下，无t(14;18)的FL中这一比例为25%（P = .016）。在有t(14;18)的DLBCL和FL中，最常见的表达模式是bcl-2+/bcl-6+。在无t(14;18)的淋巴瘤中，bcl-2和bcl-6蛋白表达之间不存在负相关关系。总之，这些数据表明，除基因重排外的其他机制可导致淋巴瘤中bcl-2和bcl-6表达失调，并且这两种蛋白之间似乎不存在如正常生发中心中所见的负相关关系。
