Tissue plasminogen activator in gastrointestinal adenocarcinoma: What is its role?

Abstract

e15532 Background: The aim of the study was a comparative analysis of the tissue plasminogen activator activity (tPA-Ag and tPA-act) in adenocarcinoma of the esophagus (EA), stomach (SA), pancreatic head (PHA), sigmoid colon (SCA) and rectum (RA). Methods: Tissues of tumors, perifocal area (PA) and resection line tissues were studied by ELISA in 143 patients (38-74 years) with EC (n = 12, G2, T2-3N0-1M0), SC (n = 28, G2, T2-3N0-1M0), PHC (n = 46, G2, Т2-4N0M0), SCC (n = 31, G2, T2-3N0-1M0) and RC (n = 26, G2, T2-3N0-1M0). Statistical analysis was performed using the Statistica 10 program. Results: Tumor levels of tPA-Ag were the highest in SA: SA˃RA˃SCA˃EA˃PHA, but in EA, SCA and RA were lower than in the resection line (p < 0.01). Tumor levels of tPA-Ag in SA were similar to the values in PA, and were 3.1-213 times higher than in other tumors. Perifocal levels of tPA-Ag were the highest in SA: SA˃SCA and RA˃EA˃PHA, but in EA and PHA they were lower than in the resection line tissues (p < 0.01), in SCA and RA – similar, in SA – exceeded the levels in all samples by 1-2 orders of magnitude (p < 0.0001). Levels of tPA-Ag were similar in resection line tissues in SCA and RA, being 2.5-128 times higher than in other tumors. The highest tPA-act was observed in perifocal and tumor tissues in SA (p < 0.0001, compared to other tumors): SA˃SCA˃RA˃EA˃PHA (p < 0.01). tPA-act in PHA tumors was 1.3 times higher (p < 0.05) than in resection line tissues and 40.5 times lower than in PA. In SCA, tPA-act was similar in tumor and PA, but was 1.3 times lower (p < 0.05) than in resection line tissues. In RA, tPA-act decreased from the resection line to the tumor by 1.3 and 2.3 times, respectively. Conclusions: The role of tPA in gastrointestinal adenocarcinomas differs: in EA, SCA and RA it has protective functions, as its levels in the tumor are lower than in the resection line. SA was accompanied by an enhanced secretion of tPA-Ag and the formation of tPA-act in tumors, with their subsequent evasion into PA. In PHA, the tPA distribution was similar, but the high rate of tPA activation led to the depletion of both forms of tPA, while still retaining their advantage in the tumor and PA, compared with the resection line.