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

Purpose: To investigate whether the level of plasminogen activator (PA) activity assayed in gastrointestinal carcinomas and the “morphologically normal tissues” adjacent to them is associated with the degree of tumor progression. Methods: Tumor and “normal tissues” were obtained from gastrointestinal surgical samples to assess urokinase-type (u-PA) and tissue-type plasminogen activator (t-PA) activities by radial caseinolytic assay and the expression of PA inhibitor-1 (PAI-1) by ELISA. We compared the PA system between the tumor and “normal tissues” and we investigated the existence of correlations between: (a) PA production in the tumor and “normal tissues”, (b) different components of the PA system, and (c) PA system and the degree of tumor progression. Results: (1) Total PA activity, u-PA activity and PAI-1 expression are significantly higher in tumor than in “normal tissues”, whereas t-PA activity does not differ between them. (2) Total PA activity mainly correlates with u-PA activity in tumor tissues and similarly with u-PA and t-PA activities in “normal tissues”. (3) There is a significant association between t-PA activity in tumor and “normal tissues” and the degree of tumor progression. Conclusions: “Morphologically normal tissues” adjacent to carcinomas present abnormal t-PA activity that is associated with the degree of tumor progression. Assaying of this activity could be useful as a predictive parameter.