Prognostic impact of plasminogen activator inhibitor type 1 expression in bladder cancer

Abstract

Recent studies have demonstrated a poor prognosis for patients who have altered expression of plasminogen activator inhibitor type 1 (PAI-1) in several cancer types. The objective of the current study was to investigate the prognostic impact of PAI-1 on patients with transitional cell carcinoma (TCC) of the urinary bladder. PAI-1 expression was quantified using real-time polymerase chain reaction in 91 TCCs and in 6 normal tissue specimens. PAI-1 concentrations were analyzed by enzyme-linked immunoadsorbent assay in plasma from 104 patients and 10 controls and in urine from 244 patients and 74 controls. PAI-1 expression was evaluated immunohistochemically in paraffin-embedded tissues (94 tumor samples and 10 adjacent normal tissue samples). The results were analyzed in relation to clinical features and follow-up. Significantly higher PAI-1 levels were detected in tissue and plasma samples, but not in urine, from patients with bladder cancer compared with controls (P=.001 and P=.008, respectively). Elevated gene expression and plasma protein concentrations were independent of tumor stage and grade. Immunostaining revealed a subgroup of patients with single tumor cells that strongly expressed PAI-1. These patients' survival was significantly shorter, and their clinical presentation was correlated significantly with lymph node-positive disease. PAI-1 gene expression in tissues and plasma protein levels were elevated in patients with TCC compared with controls. PAI-1 gene or protein expression was not associated with the clinical characteristics of bladder TCC. Although the assessment of PAI-1 expression in plasma or urine may not serve as an independent predictor of prognosis in patients with TCC, the immunohistochemical detection of single PAI-1-positive cells may serve as a predictor of survival and a possible indicator of metastasis.