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

Abstract

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 detected 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 simple inhibitor of system. uPA and PAI-2 could be new independent and strong biologically prognostic factors.