三阴性乳腺癌组织ZWINT表达及临床意义

Expression of ZWINT in triple negative breast cancer and its clinical significance

目的Zw10结合因子(Zeste white 10interactor,Zwint)在多种恶性肿瘤中高表达并与预后不良相关,但在三阴性乳腺癌(triple-negative breast cancer,TNBC)中Zwint的预后价值尚不明确。本研究旨在探讨TNBC中Zwint的表达情况及与预后的关系。方法选取2009-01-01-2013-01-01湖北医药学院附属东风医院110例TNBC患者的完整临床及病理资料。采用免疫组织化学SP法检测Zwint在TNBC组织及配对癌旁乳腺组织中的表达情况,计算细胞染色强度和阳性细胞所占比例的积分,<4为Zwint低表达组,≥4为Zwint高表达组。应用Kaplan-Meier方法及Cox模型方法分析其与TNBC临床病例特征关系及预后的意义。结果Zwint在TNBC组织的表达56.3%(62/110)高于配对癌旁乳腺组织30%(33/110),差异有统计学意义,χ^2=4.091,P=0.014;Zwint高表达与患者年龄(χ^2=2.471,P=0.116)、化疗方案(χ^2=1.349,P=0.245)、手术方式(χ^2=2.848,P=0.092)差异无统计学意义,与组织学分级(χ^2=7.990,P=0.005)、临床分期(χ^2=4.578,P=0.032)、腋窝淋巴结转移(χ^2=6.914,P=0.009)、Ki-67(χ^2=7.990,P=0.005)差异有统计学意义;随访期间,Zwint高表达组,复发、转移12例,死亡11例,Zwint低表达组,复发、转移4例,死亡4例。Kaplan-Meier生存分析显示,Zwint高表达组的中位OS为75.516(95%CI:71.199~80.853)个月,Zwint低表达组为78.545(95%CI:76.238~82.834)个月,χ^2=6.361,P=0.012;Zwint高表达组的中位DFS为63.170(95%CI:57.043~69.296)个月,Zwint低表达组为78.019(95%CI:75.548~80.489),χ^2=5.321,P=0.021。单因素Cox模型分析显示,Zwint高表达(HR=0.283,95%CI:0.090~0.892,P=0.031)、临床分期Ⅲ期(HR=0.510,95%CI:0.089~0.804,P=0.042)、组织学分级Ⅲ级(HR=1.546,95%CI:1.031~3.354,P=0.037)、腋窝淋巴结转移(HR=0.335,95%CI:0.121~0.924,P=0.035)、Ki-67高表达(HR=0.508,95%CI:0.184~0.974,P=0.025)与TNBC的预后相关,均为预后的危险因素。多因素Cox模型分析显示,Zwint高表达(HR=0.177,95%CI:0.051~0.615,P=0.006)及腋窝淋巴结转移(HR=0.174,95%CI:0.058~0.520,P=0.002)是影响患者预后的独立因素。结论Zwint高表达与TNBC患者预后相关,Zwint高表达患者预后不良,Zwint可作为TNBC患者预后预测指标及潜在治疗靶点。

OBJECTIVE The positive expression of Zwint(Zeste White 10Interactor)in kinds of malignant tumor witch often indicates poor prognosis.However,the prognosis value of Zwint in triple negative breast cancer(TNBC)is not clear yet.The aim of this study was to investigate the expression of Zwint in TNBC tissues and adjacent breast tissues and its clinical significance.METHODS Totally 110TNBC Patients treated in Dongfeng Hospital from January lst,2009to January lst,2013were selected.The expression of Zwint in cancer tissues and adjacent breast tissues were tested by imunohistochemical SP method.The sum of the staining intensity and percentage of positive cells less than 4were defined as Zwint low expression group,greaten than or equal to 4were defined as Zwint high expression group.Kaplan-Meier method was used in survival analysis,and Cox model was used to analysis the factors that might affect the prognosis of TNBC patients.RESULTS The expression of Zwint in TNBC tissues 56.3%(62/110)was significantly higher than that in adjacent breast tissues 30%(33/110),χ^2=4.091,P=0.014.The high expression of Zwint in TNBC was not correlated with patients age(χ^2=2.471,P=0.116),chemotherapy regimen(χ^2=1.349,P=0.245)and operative methods(χ^2=2.848,P=0.092),but correlated with histological grade(χ^2=7.990,P=0.005),clinical stage(χ^2=4.578,P=0.032),axillary lymph node metastasis(χ^2=6.914,P=0.009)and Ki-67expression(χ^2=7.990,P=0.005).After a median follow-up time of 53months,12patients relapsed and 11patients died of breast cancer in Zwint high expression group,4patients relapsed and 4patients died of breast cancer in Zwint low expression group.The median overall survival(OS)in Zwint high expression group was 75.516(95%CI:71.199-80.853)months,78.545(95%CI:76.238-82.834)months in Zwint low expression group,χ^2=6.361,P=0.012;The median disease free survival(DFS)in Zwint high expression group was 63.170(95%CI:57.043-69.296)months,78.019(95%CI:75.548-80.489)in Zwint low expression group,χ^2=5.321,P=0.021.For univariate Cox model analysis,the factors of OS in TNBC were Zwint high expression(HR=0.283,95%CI:0.090-0.892,P=0.031),clinical stageⅢ(HR=0.510,95%CI:0.089-0.804,P=0.042),histological gradeⅢ(HR=1.546,95%CI:1.031-3.354,P=0.037),axillary lymph node metastasis(HR=0.335,95%CI:0.121-0.924,P=0.035)and Ki-67high expression(HR=0.508,95%CI:0.184-0.974,P=0.025),all were risk factors for poor prognosis of TNBC patients.For multivariate Cox model analysis,Zwint high expression(HR=0.177,95%CI:0.051-0.615,P=0.006)and axillary lymph?x?node metastasis(HR=0.174,95%CI:0.058-0.520,P=0.002)were independent risk factors for poor prognosis of TNBC patients.CONCLUSIONS Zwint expression is associated with prognosis of TNBC,and high expression of Zwint indicates poor prognosis.Zwint is likely to be an important prognosis indicator and effective therapeutic target for TNBC.