摘要
目的探讨基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)和尿激酶型纤溶酶原激活剂(urokinase plasminogen ac-tivator,uPA)在输尿管癌组织中的表达及其对患者预后的影响。方法应用免疫组化PV两步法检测51例手术切除的原发性输尿管癌组织中MMP-9和uPA蛋白的表达和临床病理因素及预后的关系。结果 (1)51例标本中MMP-9和uPA阳性率分别为60.8%(31/51)、64.7%(33/51)。(2)MMP-9、uPA蛋白过表达存在相关性(P=0.000,r=0.835)。(3)MMP-9和uPA的表达均与年龄(P均=0.000)、临床分期(P均=0.000)、组织学分级(P=0.001,P=0.00)及病理分级(P=0.014,P=0.042)明显相关。(4)Kaplan-Meier法描绘生存曲线分析表明,MMP-9蛋白阴性组患者中位生存时间(65.00个月)明显大于阳性组(50.00个月),差异有统计学意义(P=0.00);uPA蛋白阳性组患者中位生存时间(57.00个月)明显较阴性组(65个月)短,差异亦有统计学意义(P=0.000);MMP-9阴性/uPA阴性组患者(13例)中位生存时间(65.00个月)明显高于其他组,差异有统计学意义(Log-rank检验,χ2=25.464,P=0.000)。(5)Cox比例风险模型(χ2=236.769,P=0.000)多因素分析表明:临床分期(P=0.044)、组织学分级(P=0.000)、手术方式(P=0.001)及uPA过表达(P=0.016)为影响输尿管癌预后的独立因素。结论输尿管癌组织中存在MMP-9、uPA的高表达,且两者之间的表达强度具有等级相关性,其高表达提示患者预后不良。在细胞外基质和基膜的降解过程中MMP-9和uPA可能有协同作用,最终促进肿瘤的侵袭和转移,不利于预后。联合检测二者表达可作为预测输尿管癌发生转移的危险性及患者预后情况。
Purpose To study the expression of matrix metalloproteinase-9（MMP-9） and urokinase plasminogen activator（uPA） in ureter transitional cell carcinoma（TCC） and its prognostic significance.Methods The expression of MMP-9 and uPA was examined in 51 surgical-removed specimens of primary TCC with immunohistochemical methods,correlation of these expression with prognosis of TCC was analyzed.Results Positive immunostaining for MMP-9 and uPA was observed in 60.8% and 64.7% in 51 cases of TCC,respectively.The positive expression of MMP-9 and uPA was significantly correlated in TCC（P=0.000,r=0.835）.In addition,the expression of MMP-9 and uPA was significantly correlated with age（P=0.000,P=0.000）,clinical stage（P=0.000,P=0.000）,histologic grade of lesion（P=0.001,P=0.00） and pathologic grade（P=0.014,P=0.042）.Kaplan-Meier survival analysis showed that the median survival（65.00 months） of patients with MMP-9-was significantly longer than that（50.00 months） of patients with MMP-9＋（P=0.000）.The median survival（57.00 months） of patients with uPA＋ was significantly shorter than that（65 months） of patients with uPA-（P=0.000）.The median survival（65.00 months） of 17 patients with MMP-9-/uPA-was significantly longer than that of other cases（Log-rank test,χ^225.464,P=0.000）.The Cox regress-ion model（χ^2236.769,P=0.000） analysis suggested： the clinical stage（P=0.044）,histologic grade of lesion（P=0.000）,way of surgical operation（P=0.001） and uPA overexpression（P=0.016） were independent prognostic factors for TCC.Conclusions MMP-9 and uPA are highly expressed in TCC cell,MMP-9 expression has a positive correlation with uPA expression,which indicates that the overexpression of MMP-9 and uPA may have poor prognosis for TCC patients.They may play a synergistic role in the the process of growth and invasion in TCC,and ultimately promote tumor invasion and metastasis.MMP-9 and uPA may be potential indicators of metastasis and predictors for prognosis of TCC.
出处
《临床与实验病理学杂志》
CAS
CSCD
北大核心
2012年第10期1086-1090,共5页
Chinese Journal of Clinical and Experimental Pathology
