Tissue-Type Plasminogen Activator (tPA) Content in Colorectal Cancer and in Surrounding Mucosa: Relationship with Clinicopathologic Parameters and Prognostic Significance

Abstract

The aim of this study was to evaluate the cytosolic tissue-type plasminogen activator (tPA) content in colorectal cancer, its possible relationship with the clinicopathologic parameters of tumors, and its prognostic significance. We have therefore examined by immunoenzymatic assay the cytosolic tPA content in tumors and paired surrounding normal mucosa samples from 162 colorectal 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 correlation was found between tPA content and clinicopathologic tumor parameters such as location, Dukes' stage, histologic grade, and DNA content or S-phase fraction. However, the results indicated that a high cytosolic tPA content (> 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-up period of 32.2 months. This suggests that tPA may give additional information to that provided by other biochemical markers currently used in colorectal cancer.

Lymphatic and/or blood vessel invasion in gastric cancer: relationship with clinicopathological parameters, biological factors and prognostic significance

“…In the present study we have evaluated the potential relationship between LBVI and several new biological parameters from gastric carcinomas recently associated with tumoral aggressiveness and poor prognosis, such as the tyrosine kinase receptors c-erbB-2 (Garcia et al 2003a;Vizoso et al 2004b) and EGFR (Garcia et al 2003b), the proteolytic enzymes cathepsin D (Manuel Del Casar et al 2004) and tPA (Raigoso et al 2000), the spasmolytic peptide pS2 (Suarez et al 2001;Dhar et al 2003) or the extracellular proteoglycan hyaluronic acid (Vizoso et al. 2004a).…”

Tissue-Type plasminogen activator (tPA) in breast cancer: relationship with clinicopathological parameters and prognostic significance

“…However, the clinical significance of tPA expression in tumors has been less deeply investigated. High intratumoral tPA levels have been associated with a poor prognosis in colorectal cancer [20]. By contrary, it has been reported that breast carcinomas with a high tPA content tend to have a better prognosis than those with a low, or not detectable tPA level [21][22][23], suggesting a complex role for the plasminogen activation system in human tumors.…”

Tissue-type plasminogen activator activity in morphologically normal tissues adjacent to gastrointestinal carcinomas is associated with the degree of tumor progression

“…In contrast, t-PA is currently considered to be mainly involved in intravascular fibrinolysis (Herszenyi et al 2000) and less relevance is usually given to it in tumor biology. Nevertheless, some reports suggest that t-PA is also involved in the tumor progression (Raigoso et al 2000;Sanz et al 2002;Diaz et al 2004).…”

“…Some studies, however, have yielded conflicting results about such a prognostic value (Fujii et al 1999;Raigoso et al 2000;Sanz et al 2002). It was reported that the level of t-PA activity or its expression could also have prognostic value since the low level of t-PA expression in the gastrointestinal mucosa is associated with a shorter overall survival (Verspaget et al 1995;Ganesh et al 1994Ganesh et al , 1996Ganesh et al , 1997.…”