Microncronucleus index in epithelial exfoliated cells of urothelium and buccal mucosa, and peripheral blood lymphocytes of patients with papillary urothelial carcinoma

Podrimaj-Bytyqi, Arjeta (2019) Microncronucleus index in epithelial exfoliated cells of urothelium and buccal mucosa, and peripheral blood lymphocytes of patients with papillary urothelial carcinoma. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Introduction: Bladder urothelial cell carcinoma (UCC) is an increasingly prevalent cancer worldwide, and thus, gaining a better understanding of its identifiable risk factors is a global priority. ----- Aim: This study addressed this public health need with the understanding that cancer-initiating events, such as chromosome breakage, loss and rearrangement, can be reasonably used as biomarkers to evaluate an individual’s cancer risk. ----- Methods: Overall, forty bladder cancer patients and twenty controls were evaluated for genomic instability. To the best of the investigators’ knowledge, this is the first study to perform micronucleus (MN) assays simultaneously in urothelial exfoliated cells (UEC), buccal exfoliated cells (BEC), and peripheral blood lymphocytes (PBL) in first-diagnosed, non-smoker bladder UCC patients. Additionally, the frequency of nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in PBL was evaluated. ----- Results: The MN indices in UEC, BEC, and PBL, as well as the indices of NPBs and NBUDs, were significantly higher in patients than in controls. Different levels of genomic instability were found also in relation to tumour grade and tumour muscle invasion. ----- Conclusions: MN assays, particularly in UEC, may be used to identify individuals who are at high risk of developing UCC, as single or as additional triage test to UroVysion FISH test. Our results further validate the efficacy of such biomarkers as predictors of genomic instability.

Abstract in Croatian

Uvod: Karcinom urotela mokraćnog mjehura sve je učestaliji oblik karcinoma u svijetu te je stoga bolje razumijevanje njegovih prepoznatljivih čimbenika rizika globalni prioritet. ----- Cilj rada: Ovo istraživanje se bavi tom javnozdravstvenom potrebom da se događaji koji iniciraju rak, kao što je lom, gubitak i preraspodjela kromosoma, racionalno iskoriste kao biomarkeri za procjenu rizika od karcinoma urotela. ----- Ispitanici i metode: Četrdeset bolesnika s de novo karcinomom urotela mokraćnog mjehura i dvadeset kontrolnih ispitanika analizirano je na genomsku nestabilnost. Prema dostupnim saznanjima istraživača, ovo je prva studija takve vrste koja je provela istodobno ispitivanje mikronukleusa (MN) na izljuštenim urotelnim stanicama, izljuštenim epitelnim stanicama sluznice usne šupljine i limfocitima periferne krvi bolesnika s de novo dijagnosticiranim karcinomom urotela mokraćnog mjehura. Osim toga, procijenjena je i učestalost nukleoplazmatskih mostova (NPB) i nuklearnih pupoljaka (NBUD) u limfocitima periferne krvi bolesnika i kontrolnih ispitanika. ----- Rezultati: Učestalost MN u izljuštenim urotelnim stanicama, izljuštenim epitelnim stanicama sluznice usne šupljine i limfocitima periferne krvi, kao i učestalost NPB i NBUD u limfocitima periferne krvi bila je značajno viša u bolesnika s karcinomom urotela nego li u kontrolnih ispitanika. Dodatno je utvrđen i stupanj genomske nestabilnosti u odnosu na stupanj tumora i invaziju tumorskih mišića: MN indeks bio je značajno viši u karcinomu visokoga stupnju i u invazivnom karcinomu nego u neinvazivnim podskupinama. ----- Zaključak: Testiranje mikronukleusa, a posebice na izljuštenim urotelnim stanicama, može se koristiti za otkrivanje pojedinaca koji se nalaze pod visokim rizikom za razvoj karcinoma urotela, bilo kao pojedinačni test ili kao dodatni trijažni test za UroVysion FISH test. Dobiveni rezultati dodatno potvrđuju učinkovitost analiziranih biomarkera kao prediktora genomske nestabilnosti.

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