ROLE OF PLASMA LEVEL OF PLASMINOGEN ACTIVATOR INHIBITOR TYPE 1 (PAI 1), ITS GENE POLYMORPHISM AND INHIBITOR OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR (UPA) AND UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR (UPAR) IN TUMOUR TISSUE IN COLORECTAL CARCINOMA PAT

Konference: 2008 33st Congress ESMO - účast ČR

Kategorie: Kolorektální karcinom

Téma: Colorectal cancer

Číslo abstraktu: 447

Autoři: MUDr. Jana Halámková, Ph.D.; MUDr. Igor Kiss, Ph.D.; MUDr. Zdeněk Pavlovský; Z. Čech; MUDr. Jiří Tomášek, Ph.D.; MUDr. Štěpán Tuček, PhD.; Mgr. Adam Svobodník, Ph.D.; Lada Hanákova; MUDr. Mojmír Moulis; prof. MUDr. Miroslav Penka, CSc.

Background: Urokinase (uPA) plays a fundamental role in activating plasminogen to plasmin and participates in the degradation of the elements of the extracellular matrix. Plasminogen together with its receptor (uPAR), tissue activator (tPA) and the urokinase inhibitors (PAI 1 and PAI 2) form the plasminogen activator system (PAS)which is a part of the metastatic cascade. In colorectal carcinoma some of the studies have shown that uPAR and uPA can be considered an independent prognostic factor. In our project we have researched also the gene polymorphisms PAI 1. Some studies suggest that the genotype 4G/4G could be connected with advanced stages and the polymorphism 1334G/A with higher incidence of colorectal carcinoma.

Methods: Peripheral blood samples for analysis PAI 1 and the tumour tissue were obtained from 31 patients preoperatively, or before the start of chemotherapy. Another sample was taken subsequently 4-6 weeks after from 28 patients. Analysis of gene polymorphism PAI 1 was obtained from 30 patients. The proof of uPA, uPAR, PAI 1 and PAI 2 in the tumour tissue was based on imunohistochemical reaction with polyclonal antibodies. For analysis of PAI 1 in the peripheral blood was used reaction set Spectrolyse®/pL PAI. For the need of genetic polymorphisms PAI 1 was using a standard method of ‘‘QIA Blood Mini Kit’’.

Results and conclusion: There was significant correlation between PAI 1 (p=0.011)and PAI 2 (p=0.007) in the tumour tissue and stage. In advanced cancer higher expression of uPAR in the tumour tissue was proven (p=0.005). PAI 1 plasmatic level was higher in the advanced stages before and after surgery but this increase was not statistically significant. There was significant correlation between levels of PAI 1 before and after treatment (r=0.817; p<0.001). Antigen levels of uPA, uPAR, PAI 1 and 2 were higher in advanced tumours. There was no statistical correlation between the stage of the disease and genetic polymorphisms PAI 1. For evaluation of role of PAS in colorectal carcinoma a longer follow up will be needed as well as more heterogenous group of patients.

Datum přednesení příspěvku: 12. 9. 2008