Expression of TRAF1 and Nuclear c-Rel Distinguishes Primary Mediastinal Large Cell Lymphoma From Other Types of Diffuse Large B-cell Lymphoma
Expression of TRAF1 and Nuclear c-Rel Distinguishes Primary Mediastinal Large Cell Lymphoma From Other Types of Diffuse Large B-cell Lymphoma
复制标题
TRAF1 和核 c-Rel 的表达可区分原发性纵隔大细胞淋巴瘤和其他类型的弥漫性大 B 细胞淋巴瘤
DOI：
--
复制
发表时间：
2007
影响因子：
5.6
通讯作者：
J. Kutok
中科院分区：
文献类型：
--
作者：
S. Rodig;K. Savage;A. LaCasce;A. Weng;N. Harris;M. Shipp;E. Hsi;R. Gascoyne;J. Kutok
原发性纵隔大B细胞淋巴瘤(PMLBCL)是最近发现的弥漫性大B细胞淋巴瘤(DLBCL)的一种亚型，仅凭组织学特征很难与其他类型的DLBCL区分开来。我们最近发现了一种PMLBCL的分子特征，它不同于其他形式的DLBCL，但与经典的霍奇金淋巴瘤有相同的特征。这一特征包括核因子κB(核因子κB)信号通路的激活，该通路部分通过含有核因子κB转录复合体的c-κ的核转位，以及随后肿瘤坏死因子受体相关因子-1(TRAF1)等核转录因子B靶基因的表达来发挥作用。应用标准免疫组织化学技术，检测251例大B细胞淋巴瘤(78例PMLBCL和173例其他类型DLBCL)，以确定c-rel和TRAF1的表达模式是否能可靠地区分PMLBCL和其他类型的DLBCL。在48例PMLBCL中31例(65%)和160例DLBCL中28例(18%)有强健的核c-Rel表达。此外，78例PMLBCL中48例(62%)胞浆TRAF1表达阳性，而173例DLBCL中仅20例(12%)胞浆表达TRAF1。45例PMLBCL中24例(53%)同时表达c-rel和TRAF1，而156例其他类型DLBCL中仅3例(2%)核c-rel和TRAF1同时表达。因此，结合c-rel的核定位和TRAF1的细胞表达是区分PMLBCL和DLBCL的高度特异性(特异性=98%)手段，易于应用于常规外科病理实践。
Primary mediastinal large B-cell lymphoma (PMLBCL) is a recently identified subtype of diffuse large B-cell lymphoma (DLBCL) that is difficult to distinguish from other types of DLBCL on the basis of histologic features alone. We recently identified a molecular signature of PMLBCL that is distinct from other forms of DLBCL but shares features with classical Hodgkin lymphoma. This signature includes activation of the nuclear factor κB (NFκB) signaling pathway, which in part, acts through nuclear translocation of c-Rel containing NFκB transcriptional complexes, and subsequent expression of NFκB target genes such as tumor necrosis factor receptor-associated factor-1 (TRAF1). Using standard immunohistochemical techniques, we examined 251 large B-cell lymphomas (78 cases of PMLBCL and 173 cases of other types of DLBCL) to determine whether the expression patterns of c-Rel and TRAF1 could reliably distinguish between PMLBCL and other types of DLBCL. Robust nuclear c-Rel was present in 31 of 48 (65%) cases of PMLBCL and 28 of 160 (18%) cases of DLBCL. In addition, cytoplasmic TRAF1 expression was seen in 48 of 78 (62%) cases of PMLBCL, but only 20 of 173 (12%) cases of DLBCL. Finally, the combined expression of nuclear c-Rel and TRAF1 was seen in 24 of 45 cases (53%) of PMLBCL, but in only 3 of 156 cases (2%) of other types of DLBCL. Thus, the combined nuclear localization of c-Rel and the cellular expression of TRAF1 is a highly specific (specificity=98%) means to distinguish PMLBCL from DLBCL that is readily applicable to routine surgical pathology practice.