Clinical relevance of urokinase-type plasminogen activator and its inhibitor type 1 (PAI-1) in squamous cell carcinoma of the uterine cervix

The expression of uPA and PAI-1 as parameters of tumour-associated proteolysis has been implicated in the process of tumour cell invasion and the metastatic process. However, there is limited information on the impact of these parameters in cervical carcinoma. Quantitative levels for uPA (n = 114) and PAI-1 (n = 103) were researched in operatively treated, surgically staged squamous cell cancer of the uterine cervix, using an ELISA-technique. Results were assessed regarding their impact in predicting pelvic lymph nodes metastases, tumour recurrence rate and recurrence free survival (RFS) using uni- and multivariate analysis. Median levels of both parameters were significantly higher in tumour tissue than in normal cervical tissue (p < 0.001). Detection of uPA gave no useful prognostic information. PAI-1 concentration showed a positive correlation with advanced tumour stage (p = 0.008), but no significant correlation with nodal status (pN0: 2.6 vs. pN1: 4.0 ng/mg protein; p = 0.092). Using a cut-off level of 2.4 ng/mg protein, patients with elevated PAI-1 levels demonstrated reduced RFS (45.9 versus 52.9 months; p = 0.1). Multivariate analysis, including nodal status, tumour stage, lymphovascular space involvement and grading failed to demonstrate any prognostic impact of uPA and PAI-1. The results indicate, that PAI-1 expression is of some prognostic impact in cervical cancer, indicating an association of elevated PAI levels with local tumour progression and reduced recurrence-free survival.