The study of the level of correlation between the cytokine concentration in urine and serum with pathohistological and clinical characteristics of prostate cancer

Abstract

UVOD: Karcinom prostate (KaP) u populaciji muškaraca starijih od 50 godina dolazi na drugo mesto po učestalosti . Čest uzgredni patohistološki nalaz u tkivu prostate uklonjene zbog tumora predstavlja prisustvo heterogenog ćelijskog upalnog infiltrata. Citokini produkovani od tumorskih ćelija i infiltrišućih imunskih ćelija omogućavaju preživljavanje tumorskih ćelija i njihov dalji rast. Objavljeni rezultati nekoliko studija ukazuju na povezanost vrednosti citokina iz seruma, eksprimata prostate i urina sa kliničkim i histološkim karakteristikama tumora u bolesnika sa KaP. Pokazano je da su serumske vrednosti IL-4 pojedinačni prediktor progresije bolesti i da su serumske vrednosti IL-1β i IL-12 povećane u rano otkrivenim KaP. U grupi sa malim tumorskim volumenom dominirali su HGF i IL18BP, dok su vrednosti IL18BP korelirale su sa Gleason skorom, vrednosti IL-17, GITR i ICAM-1 sa stepenom infiltracije neutrofila, a vrednosti IL18BP, IL17, GITR i ICAM-1 korelirale su sa stepenom infiltracije limfocita. IL18BP je bio prisutan u visokoj koncentraciji u uzorcima eksprimata prostate kod bolesnika sa KaP. METOD: U studiju je uključeno 88 bolesnika sa KaP i 35 zdravih osoba za dve kontrolne grupe (20 bolesnika u grupi sa benignom hiperplazijom prostate i 15 onih koji nemaju tegobe vezane za urogenitalni trakt). Nezavisne varijable su određene kliničkim karakteristikama tumora patohistološkim karakteristikama tumora i TNM stadijumom bolesti. Zavisne varijable su određene koncentracijom citokina u serumu i urinu u ispitivanim grupama. REZULTATI: Vrednosti inflamatornih citokina odražavaju stepen inflamacije u tumorskom i peritumorskom tkivu. Vrednosti hemokina odražavaju stepen infiltracije tumorskog tkiva adekvatnim tipom imunskih ćelija, koncentracija imunosupresivnih citokina odgovara veličini tumora, dok vrednosti urinarnih citokina TH1 tipa odgovoaraju stepenu limfocitne infiltracije. ZAKLjUČAK I ZNAČAJ STUDIJE: Dobijeni rezultati pružaju nove informacije o biološkim osobinama karcinoma prostate, mogućnost procene lokalnog imunskog odgovora u bolesnika sa KaP na osnovu vrednosti urinarnih citokina, pružaju mogućnost procene stepena inflamacije u tumorskom tkivu, kao i mogućnost procene efekta terapijskih procedura na lokalni imunski odgovor.INTRODUCTION: Prostate cancer (CaP) comes second in terms of frequency in the population of men older than 50. The presence of a heterogeneous cellular inflammatory infiltrate is a common incidental pathohistological finding in prostate tissue removed due to tumors. Cytokines produced by tumor cells and infiltrating immune cells enable the survival of tumor cells and their further growth. The published results of several studies indicate an association between serum cytokine values, prostate and urine excreta and clinical and histological characteristics of tumors in patients with KaP. Serum IL-4 values have been shown to be a single predictor of disease progression and serum IL-1β and IL-12 values are increased in early detected KaP. The small tumor volume group was dominated by HGF and IL18BP, while IL18BP values correlated with the Gleason score, IL-17, GITR, and ICAM-1 values with neutrophil infiltration rates, and IL18BP, IL17, GITR, and ICAM-1 values correlated with lymphocyte infiltration. IL18BP was present in high concentrations in prostate express samples in patients with KaP. METHODOLOGY: The study included 88 patients with CaP and 35 healthy individuals for two control groups (20 patients in the group with benign prostatic hyperplasia and 15 who did not have urogenital tract problems). The independent variables were determined by the clinical characteristics of the tumor, the pathohistological characteristics of the tumor and the TNM stage of the disease. The dependent variables were determined by the concentration of cytokines in the serum and urine in the examined groups. RESULTS: Inflammatory cytokine values reflect the degree of inflammation in tumor and peritumoral tissue. Chemokine values reflect the degree of infiltration of tumor tissue with an adequate type of immune cells, the concentration of immunosuppressive cytokines corresponds to the size of the tumor, while the values of urinary cytokines TH1 type correspond to the degree of lymphocytic infiltration. CONCLUSION AND THE IMPORTANCE OF THE STUDY: The obtained results provide new information on the biological properties of prostate cancer, the possibility of assessing the local immune response in patients with CaP based on urinary cytokine values, the possibility of assessing the degree of inflammation in tumor tissue, and the possibility of assessing the effect of therapeutic procedures on local immune response