Ekspresija negativnih regulatora Wnt signalnog puta u tumorima zametnih stanica testisa

master's thesis

• Title (english): Expression of negative regulators of the Wnt signaling pathway in germ cell tumors of the testis
• Author: Iris Žunić
• Mentor: Ljiljana Šerman (mentor)
• Committee member: Davor Ježek (predsjednik povjerenstva)
• Committee member: Sanja Dolanski-Babić (član povjerenstva)
• Committee member: Ljiljana Šerman (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Medical Biology); Zagreb
• Defense date and country: 2014-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Cytology, Histology and Embryology

Abstract

Obitelj proteina SFRP (od engl. secreted frizzled-related protein) najveća je obitelj Wnt signalnog puta. Dosadašnja istraživanja ukazuju na povezanost smanjene ekspresije SFRP proteina i razvoja kolorektalnog karcinoma i karcinoma urotela. Najveći postotak tumora testisa su podrijetla zametnih stanica testisa, a među njima su najčešći seminomi. Obzirom na to da SFRP proteini djeluju kao negativni regulatori Wnt signalizacije, cilj ovog rada bio je ispitivanje ekspresije SFRP1 i SFRP3 proteina u definiranoj kohorti primarnih tumora testisa, seminomskih i neseminomskih/miješanih, metodom indirektne imunohistokemije. Sakupljeni su uzorci tumora zajedno s pripadajućim zdravim tkivom koje je ujedno služilo kao pozitivna kontrola. Rezultati ekspresije oba proteina analizirani su semikvantitativno te statistički obrađeni. Dobiveni rezultati prikazuju statistički značajnu razliku ekspresije SFRP1 (seminomi=0.1 (0.7), neseminomi=0.1 (0.6), kontrola=1 (0), p<0.001) i SFRP3 proteina (seminomi=0.035 (0.3), neseminomi=0.05 (0.7), kontrola=1 (0), p<0.001) između tumorskih tkiva i kontrolnih tkiva testisa, dok razlika ekspresije između pojedinih histoloških podtipova tumora nije dokazana. Također, ne postoji značajna razlika između ekspresije SFRP1 i SFRP3 proteina s obzirom na dob pacijenata. Sukladno očekivanjima, uočavam smanjenu ekspresiju regulatora Wnt signalnog puta u tumorima u odnosu na zdravo tkivo, što upućuje na njihovu moguću ulogu u tumorigenezi tumora zametnih stanica testisa.

Abstract (english)

Secreted frizzled-related protein (SFRP) family is the largest family of Wnt signaling pathway. Current research efforts clearly outline the relationship between the decreased SFRP protein expression and develepement of colorectal and urothelial carcinomas. The highest percentages of testicular tumors are of those germline origin, among which seminomas represent the most common histotype. Taking into account that SFRP proteins act as negative regulators of Wnt signaling pathway, the purpose of this work was to determine the SFRP1 and SFRP3 protein expression in a defined cohort of primary testicular tumors (including both seminomas and non-seminomas/mixed germ cell), using immunohistochemistry. Tumor samples were collected along with the adjacent normal/benign tissue that was used as a control sample. Protein expressions were measured and the results were semiquantitively analyzed and statistically processed. Obtain results showed statistically significant difference in expression of SFRP1 (seminomas=0.1 (0.7), non-seminomas=0.1 (0.6), controls=1 (0), p<0.001) and SFRP3 proteins (seminomas=0.003 (0.3), non-seminomas=0.05 (0.7), controls=1 (0) p<0.001) between tumorous and healthy (control) tissue. The difference in expression between particular histological subtypes of tumors has not being found. Moreover, there was no significant difference between the expression of SFRP1 and SFRP3 protein in respect to patients age. We conclude that decreased expression of Wnt signaling regulators SFRP1 and SFRP3 can be observed in testicular germ cell tumors compared with normal tissue. These findings suggest their possible role in testicular germline tumorigenesis.

• Keywords: tumori zametnih stanica testisa; Wnt signalni put; SFRP1; SFRP3; imunohistokemija
• Keywords (english): testis; germ cell tumors; Wnt signaling pathway; SFRP1; SFRP3; immunohistochemistry
• Language: croatian
• URN:NBN: urn:nbn:hr:105:354884
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2015-11-23 14:15:00