Plasminogen activation system indices in basal cell carcinoma.

Abstract

e21559 Background: The plasminogen activation system plays a key role in maintaining tissue homeostasis, participating in fibrinolysis and the remodeling of the extracellular matrix and basement membranes. Its main components include plasminogen, its activators (tissue plasminogen activator [tPA] and urokinase plasminogen activator [uPA]), and their inhibitors (PAI-1, PAI-2). Under physiological conditions, the system regulates wound healing, embryogenesis, and inflammation. However, its dysregulation in pathological states, such as cancer, contributes to tumor progression, including invasion, angiogenesis, and metastasis. This study aimed to investigate the levels and activity of fibrinolytic system components (uPA, tPA, PAI-1, α₂-antiplasmin [α₂-AP], α₂-macroglobulin [α₂-MG]) in tumor tissue and the perifocal zone in superficial and solid forms of basal cell carcinoma (BCC) in men and women. Methods: The study used samples of tumor and perifocal zone tissue from 60 patients with stage I–II BCC. The control group consisted of 20 samples of intact skin obtained during plastic surgeries. Concentrations of plasmin-α₂-antiplasmin complex (PAP) and levels/activity of tPA, uPA, PAI-1, α₂-AP, and α₂-MG were determined by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using Statistica 10.0 software. Results: Tumor tissue from all patients showed a 1.5–3.9-fold increase in uPA and tPA levels and activity and a 1.5–8.9-fold increase in PAI-1 content, alongside a 1.6–2.9-fold decrease in PAP. Patients with the superficial BCC type exhibited a more than 3-fold increase in α₂-AP in tumor samples. In most cases, perifocal zone indices did not differ from control values. An exception was three male patients with the solid BCC type, in whom elevated levels and activity of uPA and tPA, increased PAI-1 content, and high PAP levels were detected in both tumor and perifocal zones. During follow-up, these patients developed local recurrences within 12–15 months. Conclusions: The data indicate an imbalance in the plasminogen activation system in BCC tissue. Elevated levels of uPA, tPA, PAI-1, and PAP in the perifocal zone suggest an expansion of the tumor’s metabolic field and the formation of a microenvironment conducive to recurrence, identifying them as potential biomarkers for predicting local relapse in basal cell carcinoma.