Courts Cornelius, Brunn Anna, Montesinos-Rongen Manuel, Siemer Dörte, Hans Volkmar, Paulus Werner, Wiestler Otmar D, Küppers Ralf, Siebert Reiner, Deckert Martina
Department of Neuropathology, University Hospital of Cologne, Cologne.
J Neuropathol Exp Neurol. 2009 Sep;68(9):972-6. doi: 10.1097/NEN.0b013e3181b31cd6.
Forkhead box P1 (FOXP1) protein is a transcription factor involved in cell signaling and regulation of gene expression. The overexpression of FOXP1 in a subgroup of systemic diffuse large B-cell lymphomas has been associated with an exceptionally poor clinical outcome. Data on FOXP1 expression in primary central nervous system lymphomas (PCNSL), that is, diffuse large B-cell lymphomas confined to the central nervous system, are not yet available. We analyzed 43 PCNSL from immunocompetent patients. Immunohistochemistry showed expression of FOXP1 protein in 21 (88%) of 24 cases. All 19 PCNSL analyzed by quantitative gene expression analysis showed overexpression of truncated FOXP1 Isoforms 3 and 9 and downregulation of normal-size FOXP1 compared with nonmalignant germinal center B cells, the normal counterpart of PCNSL tumor cells. Thus, truncated FOXP1 isoforms are preferentially overexpressed in PCNSL as they are in diffuse large B-cell lymphomas. Although the mechanisms are presently unclear, this overexpression may contribute to a poor prognosis in PCNSL.
叉头框蛋白P1(FOXP1)是一种参与细胞信号传导和基因表达调控的转录因子。FOXP1在系统性弥漫性大B细胞淋巴瘤的一个亚组中过表达,这与异常差的临床结果相关。关于原发性中枢神经系统淋巴瘤(PCNSL),即局限于中枢神经系统的弥漫性大B细胞淋巴瘤中FOXP1表达的数据尚不可得。我们分析了43例免疫功能正常患者的PCNSL。免疫组织化学显示,24例中的21例(88%)表达FOXP1蛋白。通过定量基因表达分析的所有19例PCNSL与非恶性生发中心B细胞(PCNSL肿瘤细胞的正常对应物)相比,均显示截短的FOXP1异构体3和9过表达,正常大小的FOXP1下调。因此,截短的FOXP1异构体在PCNSL中优先过表达,就像它们在弥漫性大B细胞淋巴瘤中一样。虽然目前机制尚不清楚,但这种过表达可能导致PCNSL预后不良。