Ekspresija proteina održavanja minihromozoma u keratinocitnoj intraepidermalnoj neoplaziji i invazivnom planocelularnom karcinomu kože
Expression of minichromosome maintenance proteins in keratinocytic intraepidermal neoplasia and invasive squamous cell carcinoma of the skin
Докторанд
Stojković-Filipović, JelenaМентор
Brašanac, DimitrijeЧланови комисије
Medenica, LjiljanaNikolić, Miloš
Tomanović, Nada
Tiodorović, Danica
Метаподаци
Приказ свих података о дисертацијиСажетак
Aktinična keratoza (AK) predstavlja proliferaciju neoplastično transformisanih
keratinocita ograničenih na deo epiderma i smatra se inicijalnom kliničkom
manifestacijom bolesti koja može da progredira do planocelularnog tj. skvamocelularnog
karcinoma (engl. squamous cell carcinoma, SCC), ranim stadijumom u biološkom spektru
SCC. Iz tog raloga, a prema konceptu progresije u evoluciji AK, predložena je nova
nomenklatura za AK, keratinocitna intraepidermalna neoplazija (engl. keratinocyte
intraepidermal neoplasia, KIN), prema anlanogiji sa cervikalnom intraepidermalnom
neoplazijom. Skvamocelularni karcinom kože in situ (engl. squamous cell carcinoma in
situ - SCCIS) ili Bowenova bolest (engl. Bowen disease, BD) je maligna neoplazma
ograničena na epiderm, kod koga se neoplastično tranformisani keratinociti nalaze
čitavom debljinom epiderma, bez znakova dermalne invazije. Kutani SCC je drugi
najčešći maligni tumor kože, koji se manifestuje različitim promenama od lako izlečivih,
superficija...lno invazivnih kancera do veoma infiltrovanih tumora koji metastaziraju
dovodeći do smrtnog ishoda. Može nastati de novo, ali češće nastaje iz prekursorskih
lezija, AK i SCCIS, koje, kao što je već pomenuto, prema pojedinim autorima
predstavljaju SCC u ranijim evolutivnim fazama. Iako AK, SCCIS i SCC mozemo
smatrati različitim stadijumima iste bolesti, ne progrediraju sve lezije u SCC. Molekularni
mehanizmi ove progresije još uvek nisu u potpunosti razjašnjeni.
Proteini održavanja minihromozoma (engl. minichromosome maintenance
proteins, MCM) predstavljaju kompleks proteina koji ima ključnu ulogu u regulaciji
replikacije DNK tokom ćelijskog ciklusa. MCM grupa jedarnih proteina učestvuje u
započinjanju i održavanju replikacije DNK molekula. Usklađenost funkcionalne
interakcije između MCM proteina i drugih komponenti, posredstvom protein kinaza koje
učestvuju u regulaciji ćelijskog ciklusa, omogućava početak sinteze DNK molekula samo
jednom tokom ćelijskog ciklusa, održavanjući, na taj način stabilnost genoma ćelije.
MCM proteini eksprimovani su u ćelijama u kojima je ćelijski ciklus u toku, dok se u
ćelijama koje su u stanju mirovanja i diferencijacije njihova ekspresija gubi, pa
predstavljaju potencijalno korisne markere proliferacije ćelija, posebno u tumorima...
Actinic keratosis (AK) is proliferation of a neoplastic transformed keratinocytes
confined to the epidermis and is considered as part of the initial clinical manifestation of
the disease which can progress to squamous cell carcinoma (SCC), early stage in the
biological spectrum SCC. The concept of progression with three possible steps in
evolution from AK towards SCC is defined as a keratinocyte intraepidermal neoplasia
(KIN), according to the level of epidermal involvement, analogous to cervical
intraepithelial neoplasm (CIN). Squamous cell skin carcinoma in situ (SCCIS) or
Bowen's disease (BD) is a malignant neoplasm confined to the epidermis, with fullthicknes
keratinocyte atypia, but no signs of dermal invasion. Cutaneous SCC is the
second most common malignant tumor of the skin, which is manifested as broad spectrum
of lesions, from easily curable superficial to invasive and very infiltrated tumors that
metastasize, leading to death. Although it can arise de novo, SCC, however, of...ten arises
from precursor lesions, AK and BD, which, as already mentioned, according to some
authors actually represent SCC in earlier evolutionary stages. Although AK, SCCIS and
SCC can be considered as different stages of the same disease not all the lesions
progressed in SCC. Molecular mechanisms of progression have not yet been fully
understood and explained.
Minichromosome maintenance proteins (MCM) represent a complex of proteins
that play a key role in the regulation of DNA replication during the cell cycle. MCM are
group of the nuclear proteins involved in initiation and maintenance of DNA replication.
Functional interactions between the MCM proteins and other components, by means of
protein kinases which are involved in regulation of cell cycle, allows the DNA synthesis
initiation, complete and accurate DNA replication to once per cell cycle, maintaining the
genome stability.
Expressed in cells in which the cell cycle is in progress, with lost of expression in
quiescent and differentiated cells, MCM proteins represent potentially useful markers of
cell proliferation, particularly in cancer.
The aim of this study was to investigate MCM 2, 5 and 7 expression in AK, BD
and invasive SCC, analysis of expression in situ lesions classified as keratinocyte
intraepidermal neoplasia (KIN), comparison MCM 2, MCM5 and MCM7 expression and
prognostic parameters of SCC such as size, depth of invasion, thickness and tumor grade...