Division of Hematopathology, Department of Pathology, SUNY Upstate Medical University, Syracuse, NY, USA.
J Neurooncol. 2010 Nov;100(2):249-53. doi: 10.1007/s11060-010-0188-7. Epub 2010 May 6.
Most primary central nervous system lymphomas (PCNSL) occurring in immunocompetent patients are diffuse large B-cell lymphomas (DLBCL), characterized by poor prognosis. An activated B-cell (ABC) origin of PCNSL has been postulated based on bcl-6 and MUM-1 expression by majority of these tumors. ABC DLBCL has been functionally subdivided using gene expression profiling and immunohistochemical analysis into STAT3-high and STAT-3 low subsets. A potentially crucial difference between STAT3-high and STAT3-low ABC DLBCL is in the expression of bcl-2 family members. STAT3-high cases are generally bcl-2 low and STAT3-low cases show higher expression of bcl-2. Further mechanisms such as activation of nuclear factor-kappa B (NF-κB) activation seem to be responsible for upregulation of bcl-2 in ABC subtype of DLBCL with an adverse outcome. As deregulation of STAT-3 pathway is known to play a critical role in ABC DLBCL and majority of the PCNSL are of the ABC subtype we studied the immunohistochemical expression of STAT-3 proteins in PCNSL along with other traditional markers (CD10, bcl-6, MUM-1 and bcl-2) in 17 cases of PCNSL occurring in immunocompetent patients. Despite lack of STAT3 expression in all our cases, majority (70%) of the patients with bcl-2 positive PCNSL had an adverse outcome similar to that reported in systemic lymphomas of ABC subtype. Based on our observations we propose that PCNSL represents a distinct subset of ABC diffuse large B-cell lymphomas with low STAT3 expression and perhaps mechanisms other than interaction of STAT-3 and NF-κB pathways may play a role in upregulation of bcl-2 in PCNSL. To the best of our knowledge expression of STAT-3 protein in PCNSL which represents a distinct anatomical subset of ABC DLBCL with a dismal prognosis has not been studied before.
大多数发生在免疫功能正常患者中的原发性中枢神经系统淋巴瘤（PCNSL）为弥漫性大 B 细胞淋巴瘤（DLBCL），其预后较差。大多数此类肿瘤表达 bcl-6 和 MUM-1，提示 PCNSL 起源于激活的 B 细胞（ABC）。基于基因表达谱和免疫组织化学分析，已将 ABC DLBCL 进行了功能细分，分为 STAT3 高和 STAT3 低亚群。STAT3 高和 STAT3 低 ABC DLBCL 之间的一个潜在关键区别在于 bcl-2 家族成员的表达。STAT3 高的病例通常 bcl-2 低，而 STAT3 低的病例则显示 bcl-2 表达较高。进一步的机制，如核因子-κB（NF-κB）的激活，似乎负责上调 ABC 亚型 DLBCL 中 bcl-2 的表达，从而导致不良预后。由于 STAT-3 通路的失调已知在 ABC DLBCL 中起关键作用，并且大多数 PCNSL 为 ABC 亚型，我们研究了 17 例发生在免疫功能正常患者中的 PCNSL 中 STAT-3 蛋白的免疫组织化学表达，以及其他传统标志物（CD10、bcl-6、MUM-1 和 bcl-2）。尽管我们所有病例均无 STAT3 表达，但大多数（70%）bcl-2 阳性 PCNSL 患者的预后不良与系统 ABC 亚型淋巴瘤相似。基于我们的观察结果，我们提出 PCNSL 代表具有低 STAT3 表达的 ABC 弥漫性大 B 细胞淋巴瘤的一个独特亚群，而不是 STAT-3 和 NF-κB 通路相互作用的机制可能在 PCNSL 中上调 bcl-2 中发挥作用。据我们所知，STAT-3 蛋白在 PCNSL 中的表达以前尚未在以前的研究中进行过研究，PCNSL 是 ABC DLBCL 的一个独特解剖学亚群，预后较差。
