Plasminogen activators in normal tissue and carcinomas of the human oesophagus and stomach

Abstract

Carcinogenesis in the human colon is associated with a marked increase of urokinase type plasminogen activator and a decrease of tissue type plasminogen activator. This study was performed to determine the concentrations of urokinase type plasminogen activator and tissue type plasminogen activator in normal tissue and carcinomas along the upper part of the gastrointestinal tract. Activity and antigen levels of both activators were determined in homogenates of endoscopically obtained biopsies from normal and carcinomatous tissues. Although the concentrations of tissue type plasminogen activator and urokinase type plasminogen activator in normal squamous epithelium of the oesophagus were low compared with those in columnar epithelium from the stomach, the urokinase type plasminogen activator/tissue type plasminogen activator antigen ratio of the different locations showed hardly any difference. Significant but heterogeneous increases were found in urokinase type plasminogen activator concentrations of biopsy specimens originating from carcinomas of both epithelial cell types. A decrease in tissue type plasminogen activator concentrations, as found in human colon carcinomas, could only be shown in carcinomas of columnar epithelium origin but not in squamous cell carcinomas of the oesophagus. The increase of urokinase type plasminogen activator and urokinase type plasminogen activator/tissue type plasminogen activator antigen ratio and the decrease of tissue type plasminogen activator in the carcinomas did not show a significant correlation with known prognostic determinants as differentiation grade, TNM classification, intestinal metaplasia, inflammation, and ulceration. The heterogeneous increase of urokinase type plasminogen activator in oesophageal and stomach carcinomas, together with the recently described association of urokinase type plasminogen activator in tissue extracts of breast carcinomas with aggressiveness and prognosis, may be relevance to prognostic studies, may be of relevance to prognostic studies in oesophageal and gastric cancer.