Show simple item record

Expression of proliferating cell antigens on mast cells and their significance for mast cell tumor classification

dc.contributor.advisorAleksić-Kovačević, Sanja
dc.contributor.otherJovanović, Milijan
dc.contributor.otherPopović, Nikola
dc.contributor.otherStanimirović, Zoran
dc.contributor.otherTatić, Svetislav
dc.creatorVučićević, Ivana
dc.date.accessioned2016-01-05T12:44:04Z
dc.date.available2016-01-05T12:44:04Z
dc.date.available2020-07-03T09:31:12Z
dc.date.issued2014-07-03
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=1186
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/2989
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:8062/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=45327631
dc.description.abstractKutani mastocitomi su jedna od najčešći neoplazmi pasa. Vode poreklo iz kostne srži, iz linije opredeljene za mastocite i pokazuju vrlo promenljivo ponašanje, te je predloženo nekoliko kriterijuma za nji ovu klasifikaciju, uključujući istološku gradaciju i markere proliferacije ćelija Citoplazmatska ekspresija CD117 ili KIT proteina (tirozin kinaza receptor) dovodi se u vezu sa višim stepenima maligniteta mastocitoma i lošijom prognozom Dokazano je da postoji veza između aberantne ekspresije CD117 i postojanja c-kit mutacija, iako mutacije često nisu prisutne kod svih mastocitoma sa aberantnom ekspresijom KIT proteina. Ispitivanjima su obu vaćena 24 kutana mastocitoma i 6 kontrolni uzoraka kože od 30 pasa različitog uzrasta, rase i pola. Kao pozitivna kontrola za c-kit mutaciju korišćen je izolat DNK psa sa mastocitomom za koga je ranije utvrđeno da poseduje navedenu mutaciju Uzorci tkiva fiksiranog u formalinu i ukalupljenog u parafinske blokove, bojeni su hematoksilin-eozinom i toluidin blue metodom, a imunohistohemijski na CD117, Ki-67, PCNA i CD45RA. DNK je izolovana iz istih parafinskih blokova, a primenom PCR metode i korišćenjem specifični prajmera PE1 i PE2 amplifikovan je željeni fragment DNK. Četrnaest od 24 mastocitoma su prema istološkim osobinama svrstana u mastocitome visokog stepena maligniteta, dok su preostalih deset, mastocitomi niskog stepena maligniteta. Kod 7 mastocitoma prisutno je više od šest mitotskih figura na 10 polja velikog uvećanja Prisustvo više od dve multinuklearne ćelije na 10 polja velikog uvećanja uočeno je kod 11 mastocitoma, dok su više od dve ćelije sa bizarnim jedrom na 10 polja velikog uvećanja uočene kod 10 mastocitoma. Osam mastocitoma sadrži više od 10% anaplastični mastocita sa jedrima promera oko 8-10 mikrometara. Od ukupno 24 mastocitoma, devet je Ki-67 pozitivno (7 mastocitomima višeg i 2 mastocitomima nižeg stepena maligniteta), dok se ekspresija PCNA i CD45RA uočava kod svih mastocitoma. Devet mastocitoma višeg stepena maligniteta ispoljava aberantnu citoplazmatsku ekspresiju CD117 Ni kod jednog od ispitanih uzoraka mastocitoma nije detektovano prisustvo c-kit mutacije. Prisustvo mitotskih figura, višejedarni ćelija, bizarnih jedara i kariomegalije, kao i tip ekspresije CD117 predstavljaju preduslov za novu klasifikaciju i ključne prognostičke parametre kod pasa sa mastocitomima.sr
dc.description.abstractCutaneous mast cell tumours (MCTs) are one of the most common neoplasm in dogs. Originate from the bone marrow, from the mast cells line, but because of its location are being studied within skin tumors. MCTs show a highly variable biologic behavior and therefore several criteria have been proposed for their classification, including histological grading and cell proliferation markers. Cytoplasmic expression of CD117 or KIT protein (tyrosine kinasa receptor) has been found to correlate with higher histological grade and with a worsened prognosis. It has been revealed that there is a conection between the aberrant expression of CD117 and presence of c-kit mutations, although mutations were not present in all mast cell tumors with aberrant expression of KIT protein. Twenty four MCTs and 6 control specimens from 30 dogs of different age, breed and sex were included in this study. DNA isolated from the dog with mast cell tumor which had previously found to has specified mutation was used as a positive control for c-kit mutation. Formalin fixed and paraffin embedded tissue samples were stained with hematoxylin-eosin and toluidin blue and immunohistochemically tested for CD117, Ki-67, PCNA i CD45RA expression. DNA had been extracted from the same paraffin blocks and subsequent polymerase chain reaction amplification was performed using PE1 and PE2 primers. Fourteen of 24 MCTs were histologically high-grade, while ten were classified as a low-grade malignancy. Seven MCTs have more than six mitotic figures in 10 high-power fields. The presence of more than two multinucleated cells in 10 high-power fields was observed in 11 MCTs, while more than two cells with bizarre nuclei in 10 hpf were observed in 10 MCTs. Eight MCTs have more than 10% of neoplastic mast cells with nuclei about 8-10 microns in diameter. Of the total MCTs, 9 tumors are Ki-67 positive (7 mastocytomas of high and 2 mastocytomas of low-grade malignancy), while the expression of PCNA and CD45RA was observed in all 24 MCTs. Nine MCTs of high-grade malignancy showed aberrant cytoplasm labeling for CD117. Mutations of c-kit proto-oncogene were not detected in any of the tested MCTs. The presence of mitotic figures, multinucleated cells, bizarre nuclei and karyomegaly in 10 high-power fields, as well as the pattern of CD117 expression are prerequisite for the new classification and most important prognostic factor in dogs with mast cell tumor.en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Факултет ветеринарске медицинеsr
dc.rightsopenAccessen
dc.sourceУниверзитет у Београдуsr
dc.subjectpsisr
dc.subjectdogsen
dc.subjectmast cell tumoren
dc.subjectmorphologyen
dc.subjectclassificationen
dc.subjectCD117en
dc.subjectc-kit mutationen
dc.subjectmastocitomsr
dc.subjectmorfologijasr
dc.subjectklasifikacijasr
dc.subjectCD 117sr
dc.subjectc-kit mutacijasr
dc.titleEkspresija antigena ćelijske proliferacije na mastocitima i njihov značaj za gradaciju mastocitoma pasasr
dc.titleExpression of proliferating cell antigens on mast cells and their significance for mast cell tumor classificationen
dc.typedoctoralThesis
dc.rights.licenseBY-NC-ND
dcterms.abstractAлексић-Ковачевић, Сања; Станимировић, Зоран; Поповић, Никола; Јовановић, Милијан; Татић, Светислав; Вучићевић, Ивана; Експресија антигена ћелијске пролиферације на мастоцитима и њихов значај за градацију мастоцитома паса; Експресија антигена ћелијске пролиферације на мастоцитима и њихов значај за градацију мастоцитома паса;
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/20208/Disertacija.pdf


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record