32例套细胞淋巴瘤中BTK蛋白的表达及临床意义

BTK expression and its clinical significance in 32 cases of mantle cell lymphoma

目的:检测套细胞淋巴瘤(mantle cell lymphoma,MCL)患者病理组织中Bruton酪氨酸激酶(Bruton tyrosin kinase,BTK)表达水平并分析其与患者临床特征及预后的相关性。方法:选取天津医科大学肿瘤医院2011年1月至2015年12月期间经病理检测诊断为MCL且随访资料完整的32例患者和10例良性淋巴结增生患者的病理组织。采用免疫组织化学法对32例MCL组织和10例良性淋巴结组织染色,并采用SPSS 17.0统计学软件对所收集的患者临床数据资料进行分析。结果:BTK蛋白在MCL组织和正常的淋巴组织中均呈阳性表达,但在MCL病理组织中多为强阳性表达;BTK阳性表达与Ki-67和MIPI评分相关;应用Kaplan-Meier法对预后进行分析,显示BTK强阳性表达患者的无进展生存期(progression free survival,PFS)显著低于BTK弱表达患者(P=0.030),但总生存期(overall survival,OS)无统计学意义(P=0.073);PFS的单因素分析结果显示,年龄≥65岁,ECOG评分≥2分,骨髓受累,BTK强阳性表达,Ki-67>30%,根据套细胞淋巴瘤国际预后指数(mantle cell lymphoma international prognostic index,MIPI)评分≥6分,皆是MCL患者的不良预后因素,但在Cox多因素分析结果中仅MIPI评分≥6分可作为MCL患者的独立不良预后因素。结论:BTK在MCL患者中多为强阳性表达,且与Ki-67和MIPI评分呈正相关;BTK强阳性表达患者的PFS显著低于BTK弱表达患者,但由于随访时间短暂和样本量限制,BTK的强阳性表达尚不能作为PFS的一项独立不良预后因素。

Objective： To detect Bruton tyrosin kinase（BTK） expression in patients with mantle cell lymphoma（MCL） and analyze its correlation with clinical features and prognosis. Methods： A total of 32 cases of MCL tissues and 10 cases of benign lymph nodes were sampled and stained with immunohistochemical（IHC） staining. Clinical data of these patients were analyzed using SPSS 17.0. Results：BTK was positively expressed in MCL and normal lymphoid tissues and was more strongly expressed in MCL tissue than in normal lymphoid tissue. Moreover, BTK expression level was correlated with Ki-67 and MIPI scores. Prognosis analysis showed that patients with high BTK expression exhibited shorter progression-free survival（PFS） than patients with low expression levels（P=0.030）; however, no significant difference in overall survival（OS） was observed（P=0.073）. Single-factor analysis of PFS showed that age ≥65 years, ECOG score ≥2, bone marrow involvement, strongly positive BTK expression, Ki-67 〉30%, and MIPI score ≥6 are poor prognostic factors for patients with MCL. Only MIPI score ≥6 is considered an independent poor prognostic factor in the multivariate analysis. Conclusion：BTK is strongly and positively expressed in patients with MCL, and its expression level is correlated with Ki-67 and MIPI scores. Patients with high-level BTK expression usually exhibit shorter PFS than those with low-level BTK expression; however, owing to short follow-up time and limited sample size, high-level BTK expression cannot be considered an independent poor prognostic factor for PFS.