尿激酶型纤溶酶原激活剂系统在喉癌中的表达及意义

Experssion and significance of the urokinase-type plasminogen activator and its inhibitors in squamous cell carcinoma of human larynx

目的 探讨尿激酶型纤溶酶原激活剂及其抑制剂在喉癌中的表达及与临床病理各参数及预后的关系。方法 采取免疫组化链霉卵白素生物素过氧化酶法 (labeled streptoavidin biotin peroxidase,SAB)法 ,对 10 4例喉鳞状细胞癌标本中的尿激酶型纤溶酶原激活剂 (urokinase typeplasminogenactivator,uPA)、抑制剂 (plasminogenactivatorinhibitors ,PAI)PAI 1和PAI 2表达情况进行检测。结合临床随访 ,经Kaplan Meier生存曲线、log rank检验及Cox比例风险模型分析其与临床病理参数及患者生存预后的关系。结果 uPA、PAI 1、PAI 2在喉癌组织中的表达分别为 66 3 %、70 2 %、5 0 0 %。uPA、PAI 1、PAI 2的阳性表达在颈部淋巴结转移组与非转移组中差异有显著性 ,经半定量分析P值分别为 0 0 10、0 0 2 7、0 0 3 8。单因素分析显示 :淋巴结转移及复发、肿瘤细胞分化程度、uPA和PAI 2表达是影响患者预后的因素。多因素分析提示 :淋巴结转移及复发、临床分期、uPA和PAI 2是影响患者预后的独立因素。结论 uPA在喉癌转移中起着重要的作用 ;PAI 1的作用复杂 ,可能不单纯是uPA的抑制剂 ;PAI 2可能是uPA主要抑制剂 。

Objective To detect the expression of urokinase type plasminogen activator (uPA) and its inhibitors(plasminogen activator inhibitors,PAI) type 1 and type 2 in squamous cell carcinoma of human larynx and reveal the correlation of the major clinicopathologicl parameters and prognosis Methods uPA, PAI 1 and PAI 2 were detceted from 104 cases squamous cell carcinoma of human larynx undergoing primary resection using immunohistochemistry(labeled streptoavidin biotin peroxidase, SAB) method. The results were classified positive and negative Patients were followed up prospectively for a median of 41 months(rang 24 to 84 months) Overall survival were analyzed according to Kaplan Meier and log rank statistics,the prognostic relevance of uPA, PAI 1 and PAI 2 and conventional prognostic factors were analyzed by Cox analyses Results uPA,PAI 1 and PAI 2 positivity were present both in neoplastic cells and in fibroblast cells and macrophages However, depending on the histological grading and invasive capacity of the tumor, a pronounced intra and intertumoral heterogeneity in uPA staining was observed The total positive rate of uPA, PAI 1 and PAI 2 was 66 3%, 70 2% and 50 0% respectively No relationship between the expression of these proteins and clinicopathological parameters except for lymph node metastasis and recurrence, P value was 0 010, 0 027 and 0 038 respectively Univariate survival analysis revealed a high significant inverse correlation of uPA positive expression survival time Patients with PAI 2 positive expression had a significantly longer survival time than those with PAI 2 negative expression In different clinicopathological parameters subgroups, uPA, PAI 1 and PAI 2 added significant survival information Multivariate analysis revealed that four independent prognostic factors for overall survival time were uPA, PAI 2, lymph node metastasis and recurrences and clinical stage, P =0 001, 0 002, 0 035 and 0 005 respectively Conclusion These findings suggest that uPA play important role in the metastasis of human laryngeal carcinoma and PAI 2 appears to be a true inhibitor contrary to PAI 1 PAI 1 might act as an essential modulator of the plasminogen activation system or a protector of carcinoma tissue against self degradation rather than as a simpleinhibitor of system uPA and PAI 2 could be new independent and strong biologically prognostic factors