Vol.14, No 2, 2007 pp. 47 - 52
UC 616.6:616-006
URINARY AND TISSUE BIOMARKERS IN EARLY DETECTION OF UPPER UROTHELIAL TRACT CANCER
Ivana Pešić1, Ljubinka Janković Veličković2, Dragana Stokanović3, Irena Dimov4
1Institute of Pathophysiology, Faculty of Medicine, Niš, Serbia
2Institute of Pathology, Faculty of Medicine, Niš, Serbia
3Faculty of Medicine, Niš, Serbia
4Institute of Immunology, Faculty of Medicine, Niš, Serbia
 E-mail: ikac2507@gmail.com
Summary. Upper urothelial tract cancer (UUTC) is an uncommon disease presenting only 5 to 6% of all urothelial tumors. In families affected with Balkan endemic nephropathy the incidence is 100 times greater. The most common symptom of UUTC is hematuria (75%) and flank pain (30%). Excretory urography is still the first choice examination in the exploration of hematuria. Urinary cytology testing has a high specificity (over 90%) but low sensitivity (below 50%). Flexible or rigid ureteroscopy enables taking biopsies and confirms the diagnosis with a sensitivity over 80% but with a low specificity of about 60%. This diagnostic procedure does not permit an early diagnosis, and could miss UUTC. However, the better understanding of the molecular mechanisms involved in carcinogenesis and tumor progression has provided a large number of molecular markers of UUTC, with a potential diagnostic and prognostic value. The characterization of the molecular features of urothelial carcinomas is still ongoing. The goal is to relate the tumor genotype to am individual's phenotype and to discover a specific diagnostic marker associated to the tumor's molecular biology. If an at-risk genetic profile could be established, it might be possible to predict, even prevent urothelial carcinomas in some patients. Further investigations are needed in order to find the best marker for early detection of UUTC. The ideal UUTC test is still unavailable, but the eventual "gold standard" will consist of multiple assays that analyze nucleic acids and proteins for detection. In addition, these tests would also reveal to the clinician both prognostic information and therapeutic targets for personalized medical treatment.
Key words: Upper urothelial tract cancer, biomarkers, diagnosis, prognosis
URINARNI I TKIVNI BIOMARKERI U RANOJ DIJAGNOSTICI KARCINOMA GORNJEG URINARNOG TRAKTA
Kratak sadržaj: Karcinom gornjeg urinarnog trakta (UUTC) je retko oboljenje koje predstavlja samo 5 do 6% svih urotelijalnih tumora. Incidenca tumora je 100 puta veća u porodicama obolelih od Balkanske endemske nefropatije. Najčešći simptomi UUTC-a su hematurija (75%) i bol u slabinama (30%). Ekskretorna urografija je još uvek metoda izbora u ispitivanju hematurije. Urinarna citologija pokazuje visoku specifičnost (preko 90%) ali nisku senzitivnost (ispod 50%). Fleksibilna ili rigidna ureteroskopija omogućava biopsiju i služi za potvrđivanje dijagnoze sa senzitivnošću preko 80% ali niskom specifićnošću oko 60%. Ove dijagnostičke procedure ne omogućavaju ranu dijagnostiku, i mogu da propuste UUTC. Međutim, bolje razumevanje molekularnih mehanizama uključenih u procese karcinogeneze i razvoja tumora donosi veliki broj potencijalnih molekularnih markera UUTC-a, sa potencijalnom prognostičkom i dijagnostičkom vrednošću. Ispitivanje molekularnih karakteristika urotelijalnih karcinoma je u toku, sa ciljem da se otkrije veza između genotipa tumora sa individualnim fenotipom i da se otkrije specifičan dijagnostički marker koji je udružen sa molekularnom biologijom tumora. Ako bi se ustanovio genetski profil sa rizikom, bilo bi moguće predvideti ćak i sprečiti razvoj urotelialnog karcinoma kod određenih pacijenata. Dalja israživanja su neophodna sa ciljem da se pronađe najbolji marker za ranu detekciju UUTC-a. Idealni UUTC test još uvek nije dostupan, te eventualni "zlatni standard" bi predstavljao multiple eseje koji analiziraju nukleinske kiseline i detektuju proteine. Pored toga, ovi testovi bi pružali kliničarima istovremeno informacije o prognozi i individualnom terapijskom pristupu.
Ključne reči: Karcinom gornjeg urinarnog trakta, biomarkeri, dijagnoza, prognoza