bcl-2蛋白及分类模型在弥漫性大B细胞淋巴瘤中的预后意义

Clinical significance of bcl-2 protein expression and classification algorithm in diffuse large B-cell lymphoma

目的探讨bcl-2蛋白表达以及Hans、Chan及Muris分类模型对弥漫性大B细胞淋巴瘤（DLBCL）预后的提示意义。方法收集常规及会诊的237例DLBCL患者病例，对其石蜡切片行免疫组织化学EnVision法染色，检测Ki-67、CD3、CD45RO、CD20、CD79a、bcl-2、bcl-6、CD10、MUM-1、GCET-1、FOXP-1的表达。使用Hans、Chan及Muris分类模型进行分组并结合临床数据进行分析。结果男性131例，女性106例，平均年龄52．6岁。淋巴结发病最为常见（31．6％，75／237），结外发病以胃肠道（45．2％，71／157）为多见。Ki-67、CD3、CD45RO、CD20、CD79a、bcl-2阳性率分别为96．4％（215／223）、0、14．5％（11／76）、99．1％（231／233）、81．7％（85／104）、61．5％（139／226），分类标志物GCET-1、CD10、bcl-6、MUM-1及FOXP-1阳性率分别为27．9％（43／154）、24．8％（57／230）、50．2％（116／231）、46．3％（105／227）、80．2％（142／177）。患者均有完整随访资料，中位生存期为103．9个月，3年生存率51．3％（98／191）。bcl-2阴性组预后明显好于阳性组（P=0．019）。230例按Hans模型分组，95例为生发中心B细胞（GCB）组，135例为非GCB组，两组预后差异无统计学意义（P=0．102）；181例按Chan模型分组，68例为GCB组，113例为非GCB组，GCB组预后明显好于非GCB组（P=0．031）。218例按Muffs模型分组，154例为Groupl组，64例为Group2组，Groupl组预后明显好于Group2组（P=0．023）。bcl-2与Chan模型结合分组，bel-2蛋白在非GCB组中表达明显增高（P=0．028），非GCB中bcl-2阳性表达组预后最差，GCB中bcl-2阴性表达组预后最好，不同分组预后差异有统计学意义（P〈0．05）。结论国人DLBCL以非GCB更为常见，bel-2蛋白在非GCB组中表达明显增高。bel-2蛋白表达、Chan模型及Muris模型具有预后提示意义，bcl-2结合Chan模型是目前临床上明确肿瘤细胞起源、提示临床预后的最佳组合。

Objective To investigate the clinical significance of bcl-2 protein expression and three classification algorithms including Hans model, Chan model and Muris model in patients with diffuse large B-cell lymphoma （DLBCL）. Methods Two-hundred and thirty-seven cases were collected. Standard two- step EnVision method of immunohistochemical staining was used to assess the expression of Ki-67, CD3, CIMSRO, CD20, CD79a, bcl-2, bcl-6, CD10, MUM-l, GCET-1, and FOXP-1. The phenotypic classifications were assessed according to the standard of the three models. Results The male（ 131 cases） to female（ 106 cases） ratio was about 1.24： 1, the average age was 52. 6 years. Seventy-five cases （31.6% , 75/237） showed primarily lymph node involvement. Gastrointestinal tract （71 cases ） was the most commonly involved extra-nodal organ. All cases expressed one or more pan B cell markers such as CD20 （99. 1%, 231/233）. All patients with complete clinical follow-up data survived from 1-120 months. The expression of bcl-2 protein indicated an adverse prognosis（P = 0. 019）. Two-hundred and thirty cases were classified according to Hans model, with ninety five GCB cases and one-hundred and thirty five non-GCB cases. Survival analysis showed no difference between GCB and non-GCB subtypes（P = 0. 102）. Accordingto the Chan＇s algorithm, sixty eight case of one-hundred and eighty one were belong to GCB group, with one- hundred and thirteen non-GCB cases. GCB subtype showed much better prognosis than non-GCB subtype according to survival analysis （ P = 0. 031 ）. Additionally, bcl-2 protein expression in non-GCB subtype showed the worst survival. In Muris＇ model, 154 of 218 cases were classified as Group 1, while 64 cases were classified as Group 2. Group 1 showed better prognosis than Group 2 （ P 〈 0.05 ）. Conclusions Non-GCB group is the more common type of DLBCL in China. High expression of bcl-2 protein is detected in the non-GCB group. Not all subgroups classified with different classification models indicate different prognosis. Bcl-2 expression combined with Chan＇s algorithm may be the best tool to predict outcome.