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
摘要目的 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Muris模型分组,154例为Group1组,64例为Group2组,Group1组预后明显好于Group2组(P=0.023).bcl-2与Chan模型结合分组,bcl-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,bcl-2蛋白在非GCB组中表达明显增高.bcl-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.
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abstractsObjective 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,CD45RO,CD20,CD79a,bcl-2,bcl-6,CD10,MUM-1,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).According to 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.
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