Tissue-type plasminogen activator (tPA) content in colorectal cancer and in surrounding mucosa: relationship with clinicopathologic parameters and prognostic significance

The aim of this study was to evaluate the cytosolic tissue-type plasminogen activator (tPA) content in color-ectal cancer; its possible relationship w ith the clinicopathologic parameters of tumors, and its prognostic signific ance. We have therefore examined by immunoenzymatic assay the cytosolic tPA content in tumors and paired surrounding normal mucosa samples from 162 co lorectal cancer patients. Cytosolic tPA levels were significantly higher in surrounding normal mucosa samples than in neoplastic tissues (4.01+/-5.07 vs 2.63+/-5.82 ng/mg protein; p<0.0001). By contrast, no significant correl ation was found between tPA content and clinicopathologic tumor parameters such as location, Dukes' stage, histologic grade, and DNA content or S-phas e fraction. However, the results indicated that a high cytosolic tPA conten t (>0.75 ng/mg protein) in tumors predicted for a shorter relapse-free and overall survival (both p<0.05) in 123 resectable colorectal cancer patients who were prospectively evaluated during a mean follow-clp period of 32.2 m onths. This suggests that tPA may give additional information to that provi ded by other biochemical markers currently used in colorectal cancer.