survivin、bcl-2及ki-67在弥漫大B细胞淋巴瘤中的表达及临床意义

Expression and clinical significance of survivin, bcl-2, and ki-67 protein expression in diffuse large B cell lymphoma

目的:研究弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)对化疗不敏感和复发现象是否与凋亡抑制因子survivin、bcl-2蛋白及增殖因子ki-67蛋白的表达有关。方法:收集2000-2003年本院收治的经病理学证实的DLBCL患者,符合入组条件41例,分析IPI各因素及疗效与预后之间的相关性。同时,20例可获取病理组织标本的患者,用免疫组化方法进行survivin、bcl-2及ki-67蛋白表达的测定,并对其进行预后相关性分析。结果:单因素分析显示临床分期、结外侵犯情况、ECOG评分、血清乳酸脱氢酶水平及疗效均为DLBCL的独立预后因素,是否合并放疗或使用美罗华对预后影响无统计学差别;多因素分析提示ECOG评分与疗效是影响无进展生存的独立预后因素。免疫组化分析显示ki-67乘积高的患者生存期较短(P<0．05),复发组的平均ki-67指数及bcl-2乘积较未复发组高(前者P<0．05,后者P=0．069),bcl-2乘积高的患者死亡率较高(P<0．05),survivin核阳性患者较核阴性患者生存期短,但差异未达到统计学意义(P>0．05)。结论:临床分期、结外侵犯情况、ECOG评分、血清乳酸脱氢酶水平、疗效及ki-67均为DLBCL的独立预后因素,Ki-67指数高为复发危险因素,bcl-一2乘积高为预后危险因素,survivin核阳性可能是预后不良因素。

Objective：To study the expression of survivin, bcl-2 and Ki-67 proteins and analyze their prognostic significance for chemotherapy insensitivity and recurrence of diffuse large B cell lymphomas （DLBCL）. Methods： Forty-one patients with DLBCL confirmed by pathological examination between 2000 and 2003 in our hospital were recruited in this study. The correla tion analysis was performed between international prognostic index and prognosis. The specimen was collected from 20 patients. The expressions of survivin, bcl-2, and Ki-67 proteins was tested by immunohistochemical （IHC） method and correlated with survival rate. Results： Univariate analysis showed that clinical stage, extranodal invasion, ECOG performance status, LDH level, and clinical efficacy were independent prognostic factors for progression-free survival （PFS）. Combined treatment with radiotherapy and rituxan had no influence on prognosis. Multivariate analysis indicated ECOG performance status and clinical efficacy were independent prognostic factors for PFS. Immunohistochemical analysis demonstrated patients with high Ki-67 index had shorter survival time （P〈0.05）. The recurrence group had higher Ki67 index and bcl-2 expression （P〈0.05 and P=0.069）. The mortality rate was higher in patients with increased bcl-2 expression （P〈0.05）. The survival time had the tendency to be short in the patients with survivin nuclear translocation than those without nuclear translocation, but the difference was not significant （P〉0.05）. Conclusion：Clinical stage, extranodal invasion, ECOG performance status,LDH level, clinical efficacy, and Ki-67 are independent prognostic factors for DLBCL. High Ki- 67 index was a risk factor for recurrence and high bcl-2 expression was a risk factor for prognosis. Nuclear positivity of survivin indicated poor prognosis.