p-AXL与c-MYC和/或BCL-2共表达在弥漫大B细胞性淋巴瘤中的临床意义

Clinical Significance of Expression of p-AXL and Co-expression with c-MYC and/or BCL-2 in DLBCL

【目的】探索磷酸化酪氨酸激酶p-AXL在弥漫大B细胞性淋巴瘤(DLBCL)中的表达情况及其临床病理意义,并进一步探讨p-AXL与c-MYC和/或BCL-2共表达的临床病理意义,及其与MYC断裂基因的临床病理联系。【方法】收集2012-2017年在中山大学附属第一医院确诊为DLBCL的病例118例,将入组的石蜡组织制作成组织芯片。免疫组化法检测DLBCL组织中p-AXL、c-MYC和BCL-2蛋白的表达;荧光原位杂交法(FISH)检测DLBCL组织中MYC断裂基因的表达情况。【结果】p-AXL蛋白在DLBCL肿瘤细胞的胞膜和/或胞质中表达;p-AXL表达与DLBCL化疗缓解呈显著性相关(P<0.01),阳性患者化疗缓解率低于阴性患者;p-AXL表达与Hans分型显著性相关(P<0.01),p-AXL多见于Non-GCB型;p-AXL与c-MYC、BCL-2及c-MYC/BCL-2蛋白表达均显著性相关(P<0.01)。p-AXL/c-MYC、p-AXL/BCL-2、p-AXL/c-MYC/BCL-2蛋白共表达均与Hans分型显著性相关(P<0.01),多见于Non-GCB型。p-AXL与患者无进展生存期(PFS)显著性相关,阳性者PFS低于阴性患者(P<0.05);p-AXL阳性者总生存期(OS)亦低于p-AXL阴性者,但差异未达统计学意义(P>0.05)。单变量分析显示,男性且p-AXL阳性、Non-GCB型且p-AXL阳性、p-AXL/c-MYC、p-AXL/c-MYC/BCL-2蛋白共表达均是DLBCL患者PFS和OS降低的危险因素(P<0.05);但是,多变量分析显示,仅男性且p-AXL阳性、p-AXL/c-MYC蛋白共表达是DLBCL患者PFS和OS降低的显著性危险因素(P<0.05;P<0.01)。【结论】DLBCL中p-AXL与c-MYC和/或BCL-2的表达、Hans分型、肿瘤化疗缓解率降低和PFS缩短均显著性相关;p-AXL/c-MYC共表达、男性且p-AXL阳性均可作为DLBCL的独立性预后指标。

【Objective】To investigate the expression and significance of phosphorylated receptor tyrosine kinase(p-AXL)in diffuse large B cell lymphoma(DLBCL),and the clinical value of its co-expression with BCL-2 and/or c-MYC split gene.【Methods】Totally 118 cases of DLBCL were collected in the First Affiliated Hospital of Sun Yat-sen University from 2012 to 2017,and prepared as tissue array.p-AXL,c-MYC and BCL-2 proteins were detected by immunohistochem⁃istry,and c-MYC split gene was detected by FISH staining.【Results】p-AXL protein was stained on tumor cells’mem⁃brane or in the cytoplasm of DLBCL cells.p-AXL was expressed more commonly in Non-GCB type than in GCB type.The expression of p-AXL was significantly correlated with the chemotherapy effect(P<0.01),and the expression of c-MYC split gene or BCL-2 protein separately(P<0.01).Co-expression of p-AXL and c-MYC,or BCL-2,or both of them was significantly correlated with the Hans typing(P<0.01).The PFS of p-AXL positive patients was obviously lower than that of p-AXL negative patients(P<0.05).The OS of p-AXL positive patients was also lower than that of the negative patients,but the difference had no statistical significance(P>0.05).Univariate analysis showed that p-AXL and male,p-AXL and Non-GCB type,p-AXL and c-MYC co-expression,p-AXL and c-MYC and/or BCL-2 co-expression were the risk fac⁃tors for PFS and OS in DLBCL patients(P<0.05).Multivariate analysis showed that p-AXL positive in male(P<0.05)and p-AXL/c-MYC co-expression(P<0.01)were independent risk factors for PFS and OS in DLBCL patients.【Conclusions】p-AXL protein is expressed in DLBCL,and its expression is significantly related to the expression of c-MYC and BCL-2.p-AXL expression is associated with lower chemotherapy response rate,shorter progression-free survival and shorter over⁃all survival.p-AXL/c-MYC co-expression or p-AXL positive in male may be an independent prognostic factor for DLBCL patients.