尿激酶型纤溶酶原激活剂及其抑制剂在喉癌患者预后中的价值

目的:评估尿激酶型纤溶酶原激活剂(uPA)及其抑制剂(PAI-1、PAI-2)在喉癌中的表达是否具有临床预后价值。方法:通过免疫组化法检测127例喉癌患者uPA、PAI-1、PAI-2的抗原表达情况并经半定量分析结合临床随访,经Kaplan-Meier生存曲线、log-rank检验及Cox比例风险模型分析它们与临床病理参数之间及患者预后的关系。结果:单因素分析表明在传统的预后指标中只有肿瘤细胞的分化状态、淋巴结转移及肿瘤细胞生长方式与预后有关(P<0.05);uPA抗原阳性表达者生存时间缩短,PAI-2阳性表达者预后较好(P<0.01);在T1+2组中uPA阳性者生存率明显降低;uPA-阳性/PAI-2-阴性强烈提示患者预后不佳。经Cox分析发现uPA、PAI-2、淋巴结转移及肿瘤的分化状态是影响喉癌患者生存的独立危险因素。结论:uPA系统在喉癌浸润转移中起着重要的作用,uPA、PAI-2是喉癌患者新的独立的生物学预后指标。uPA有助于评估转移的潜在危险性,并对筛选早期高危险喉癌患者有重要意义。

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

Objective;The aim of the present study was to evaluate whether the expression of uPA parameters might he of clinical value in squamous cell carcinoma of human larynx as a tumor/biologically defined risk factor. Method: In a consecutive series of 127 patients resected for primary squamous cell carcinoma of human larynx, the expression of uPA and plasminogen activator inhibitors( PAD type- 1, type-2 was determined immunohistochemical-ly. The results were classified as positive and negative. Patients were followed-up prospectively for a median of 41 months(rang 6 to 84 months). Overall survival were analyzed according to Kaplan-Meier and log-rank statistics, the prognostic relevance of uPA,PAI-l ,PAI-2 and conventional prognostic factors were analyzed by Cox analyses. Result; These revealed a high significant inverse correlation of uPA positive expression survival time( P =0. 006); and patients with PAI-2 positive expression had a significantly longer survival time than those with PAI-2 negative expression( P =0.009); in different clinicopathological parameters subgroups uPA,PAI-2 added significant survival information, whereas PAI-1 positive expression did not associate with prognoses. Patients with uPA-pasi-tive/PAI-2-negative expression had the poorest prognoses. Multivariate analysis revealed that four independent prognostic factors for overall survival time were uPA , PAI-2 , lymph node metastasis and differentiation of tumor, P =0. 0002,0. 0001,0. 0117,0. 0436 respectively, relative risk and 95% confidence interval were 1.99(1.39 to 2. 85),0. 36(0. 212 to 0. 609) ,2. 36(1. 21 to 4. 61X1. 51 (1. 01 to 2. 25) respectively. Conclusion; We conclude that uPA and PAI-2 are new independent and strong biologically prognostic factors, uPA positive expression may be a powerful aid in evaluating metastatic potential and high risk patients in early stage of human larynx carcinoma.