Prognostička vrijednost imunohistokemijske ekspresije 8-okso-7,8-dihidro-2'-deoksigvanozina u bolesnika s kolorektalnim karcinomom [Prognostic value of 8-oxo-7,8dihydro-2'-deoxyguanosine immunohistochemical expression in patients with colorectal cancer ]

Matošević, Petar (2015) Prognostička vrijednost imunohistokemijske ekspresije 8-okso-7,8-dihidro-2'-deoksigvanozina u bolesnika s kolorektalnim karcinomom [Prognostic value of 8-oxo-7,8dihydro-2'-deoxyguanosine immunohistochemical expression in patients with colorectal cancer ]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Abstract: Role of the oxidative stress in the carcinogenesis of colorectal cancer is still unclear. 8-oxo-7,8-dihydro-2´-deoxyguanosine (8-oxodG) is a marker of deoxyribonucleic acid (DNA) damage and a potential marker for carcinogenesis. The hypothesis of this study is that increased expression of 8-oxo-7,8-dihydro-2´- deoxyguanosine in colorectal cancer is associated with higher tumor stage and shorter overall survival. The aim of this study was to identify 8-oxodG by immunohistochemistry in tumor tissue and surrounding normal mucosa in patients with colorectal cancer and to find out if its expression correlates with survival, depending on the stage of the disease according to the IUCC classification. The study was conducted on samples of patients operated for colorectal cancer at the Department of Surgery, University Hospital Center Zagreb, between January 1999 and December 2000. A total of 146 patients were identified and 8 were excluded due to lack of clinical data on disease progress. The final results were thus obtained by analyzing data of 138 patients. The study proved the relationship between the presence of 8-oxodG and worse survival in patients who underwent colorectal cancer surgery. Higher percentage of 8-oxodG positive tumors cells correlated with advanced disease stage. A positive correlation of the intensity of 8-oxodG reaction with advanced disease stage was not found. This can be explained by the relatively small number of patients, especially after dividing the cohort along various stages of the IUCC classification. Larger prospective studies are therefore needed to explain the effect of oxidative stress on the process of carcinogenesis in patients with colorectal cancer.

Abstract in Croatian

Oksidativni stres ima nepotpuno razjašnjenu ulogu u karcinogenezi kolorektalnog karcinoma. 8-oxo-7,8-dihidro-2´-deoksigvanozin (8-oxodG) marker je oštećenja 2- deoksigvanozina u sklopu deoksiribonukleinske kiseline (DNK) i potencijalni biljeg za karcinogenezu. Potvrđena je hipoteza ovog istraživanja da je pojačana ekspresija 8- oxo-7,8-dihidro-2´-deoksigvanozina u tumorskim stanicama kolorektalnog karcinoma povezana s višim stadijem tumora i kraćim ukupnim preživljenjem bolesnika. Cilj ovog istraživanja bio je identificirati 8-oxodG u tumorskom tkivu i normalnoj okolnoj sluznici u bolesnika s kolorektalnim karcinomom imunohistokemijskom metodom, te povezati s preživljenjem bolesnika oboljelih od kolorektalnog karcinomoma, ovisno o stadiju bolesti po TNM klasifikaciji. Istraživanje je provedeno na uzorcima bolesnika s patohistološkom dijagnozom kolorektalnog karcinoma, operiranih u Klinici za kirurgiju, KBC Zagreb, u razdoblju od dvije godine (1.1.1999. do 31.12.2000. godine) za koje postoje podaci o kliničkom praćenju. Ukupan broj bolesnika uključenih u ovu studiju bio je 146, konačni rezultati dobiveni su analizom podataka 138 bolesnika, dok je 8 bolesnika isključeno iz studije radi nedostatka kliničkih podataka o tijeku bolesti. U istraživanju je dokazana povezanost prisutnosti 8-oxodG s lošijom preživljenjem bolesnika operiranih zbog kolorektalnog karcinoma. Dokazana povezanost većeg postotka pozitivnih stanica na 8-oxodG s uznapredovalim stadijem bolesti. Nije potvrđena pozitivna korelacija intenziteta reakcija na 8-oxodG i višeg stadija bolesti. Takav rezultat može se objasniti relativno malim brojem bolesnika uključenih u studiju, osobito nakon podjele po skupinama unutar različitih stadija bolesti. Stoga bi buduće prospektivne studije na većem broju bolesnika mogle pokušati objasniti učinak oksidativnog stresa na proces karcinogeneze u bolesnika s kolorektalnim karcinomom.

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