Ekspresija proteina visoke mobilnosti grupe A (HMGA) i njihovih modulatora u keratinocitnoj intraepidermalnoj neoplaziji i invazivnom planocelularnom karcinomu kože
Expression of high mobility group A (HMGA) proteins and their modulators in keratinocytic intraepidermal neoplasia and invasive squamous cell carcinoma of the skin
Doktorand
Bosić, Martina M.Mentor
Brašanac, DimitrijeČlanovi komisije
Marković-Lipkovski, JasminaLabudović-Borović, Milica
Đuričić, Slavica
Metapodaci
Prikaz svih podataka o disertacijiSažetak
Uvod: Skvamocelularni karcinom kože (engl Squamous cell carcinoma, SCC) je drugi
najĉešći maligni tumor kože. Solarna tj. aktiniĉna keratoza (AK) i in situ SCC, odnosno
Bowen-ova bolest (engl. Bowen’s disease, BD) predstavljaju intraepidermalnu
proliferaciju neoplastiĉnih / displastiĉnih keratinocita. Iako bi AK, BD i SCC mogli
predstavljati razliĉite stadijume iste bolesti samo mali broj AK progredira u SCC.
Molekularni mehanizmi ove progresije nisu u potpunosti razjašnjeni. Proteini visoke
mobilnosti grupe A1a/1b i A2 (High mobility group protein A1a/1b i A2, HMGA1a/1b i
HMGA2) i njihovi modulatori protein arginin metiltransferaze (PRMT1 i PRMT6), p300 i
p300/CBP udruženi faktor (p300/CBP associated factor, PCAF) imaju ulogu
transkripcionih faktora i posttranslacionih modulatora, te bi mogli imati ulogu u
kancerogenezi epidermalnih tumora.
Ciljevi: Cilj studije bio je da se utvrde razlike u ekspresiji HMGA1a/1b i HMGA2 proteina
i njihovih modulatora PRMT1, PRMT6, p300 i PCAF izmeĊu A...K, BD i SCC, u in situ
lezijama klasifikovanim kao keratinocitna intraepidermalna neoplazija (KIN), kao i u
odnosu na prognostiĉke parametre SCC kože (dimenzije, debljina, dubina invazije i gradus
tumora).
Materijal i metode: Istraživanje je sprovedeno na 90 AK, 50 BD i 167 sluĉajeva SCC kože,
meĊu kojima je bilo 57 dobro, 55 srednje i 55 slabo diferentovanih tumora. Ekspresija
HMGA1a/1b, HMGA2, PRMT1, PRMT6, p300 i PCAF proteina je ispitivana
imunohistohemijski. Analizirani su broj pozitivnih ćelija tj. obim ekspresije
(semikvantitativno) i distribucija imunopozitivnosti...
Introduction: Cutaneous squamous cell carcinoma (SCC) is the second most common
malignant cutaneous tumour Actinic keratosis (AK) and in situ SCC (also known as
Bowen’s disease, BD) represent intraepidermal proliferation of neoplastic / dysplastic
keratinocytes. Although AK, BD and SCC could represent different stages of the same
disease, only small number of AK will progress to SCC. Molecular mechanisms of this
progression are not fully understood. High mobility group Aa/1b and A2 proteins
(HMGA1a/1b and HMGA2), as well as their modulators protein arginin methyltransferases
(PRMT1 and PRMT6), p300 and p300/CBP associated factor (PCAF) act as transcriptional
factors and posttranslational modulators. Thus they could play important role in
cancerogenesis of epidermal tumors.
Aims: The aim of study was to evaluate differences in expression of HMGA1a/1b and
HMGA2 proteins and their modulators PRMT1, PRMT6, p300 and PCAF between AK,
BD and SCC, in situ lesions classified as keratinocytic in...traepidermal neoplasia (KIN), as
well as in relation to prognostic parameters of cutaneous SCC (tumor diameter, thickness,
level of invasion and its differentiation).
Material and methods: In this study, 90 AK, 50 BD i 167 cases of cutaneous SCC, among
which 57 well, 55 moderately and 55 poorly differentiated tumors, were included.
Expression of HMGA1a/1b, HMGA2, PRMT1, PRMT6, p300 and PCAF proteins was
evaluated using immunohistochemical means. Number of positive cells (level of
immunopositivity, evaluated in a semiquantitative manner) and distribution of positive
cells were examined.
Results: HMGA1a/1b expression was often present in SCC compared to AK and BD, as
well as in well- and moderately differentiated SCC...
Fakultet:
Универзитет у Београду, Медицински факултетDatum odbrane:
14-07-2016Projekti:
- Molekulski prognostički markeri i epigenetska kontrola u tumorima kože i regije glave i vrata (RS-MESTD-Basic Research (BR or ON)-175026)