Uloga ćelijske senescencije indukovane onkogenima u malignoj transformaciji i progresiji tumora dojke
The role of oncogene-induced senescence in malignant transformation and breast tumor progression
Author
Jovanović, DaliborMentor
Mitrović, SlobodankaCommittee members
Stanković, VesnaMijović, Milica
Spasić, Marko
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Show full item recordAbstract
Uprkos značaju pojedinih prognostičkih faktora, njihova tačnost u proceni
ishoda i određivanju strategija lečenja obolelih od karcinoma dojke je ograničena.
Stoga bi definisanje novih molekularnih biomarkera moglo pružiti pouzdaniji
pristup u predviđanju prognoze ove bolesti.
Cilj ove studije je ispitivanje ekspresije markera p16, p53, p21, pRb i GLB1 u
benignim i malignim promenama dojke, kao i njihovog učešća u malignoj
transformaciji.
Istraživanje je obuhvatilo analizu tkivnog materijala benignih i malignih
promena pacijentkinja operisanih u UKC Kragujevac. Na H&E obojenim preparatima
definisani su svi makro i mikromorfološki prognostički faktori (histološki tip
i gradus tumora, veličina, nodalni status, dezmoplazija, nekroza, mononuklearna
reakcija i td.) Imunohistohemijski, primenom antitela (p16,p53,p21,pRb,GLB1),
određivana je tkivna ekspresija markera semikvantitativnim očitavanjem pozitivne
reakcije. Definisanjem cut off vrednosti, karcinomi su svrstavani u pozitivnu i
negativ...nu grupu za svaki analizirani marker.
Ekspresija svih markera raste sa progresijom citoloških promena u epitelu.
Njihova ekspresija je u pozitivnoj korelaciji sa različitim promenama u dojci, sa
proliferativnim indeksom i HER2+ tumorima. Ekspresija p16, pRb, p21, GLB1 je
najveća u HER2+ karcinomima dojke, dok je ekspresija p53 najveća u TNBC. Značajna
korelacija je utvrđena između ekspresije p16 i p53, p21 i pRb, p21 i GLB1, kao i
između pRb i GLB1 u invazivnom karcinomu.
Analizirani markeri igraju važnu ulogu u proliferaciji, malignoj
transformaciji, kao i u progresiji karcinoma dojke, što ih preproručuje za dalja
istraživanja i moguće korišćenje u dijagnostičke, prognostičke i prediktivne svrhe.
Despite the importance of certain prognostic factors, their accuracy in assessing
outcomes and determining treatment strategies for breast cancer patients is limited. Therefore,
the definition of new molecular biomarkers could provide a more reliable approach for
prediction of the prognosis of this disease.
The aim of this study was to examine the expression of markers p16, p53, p21, pRb
and GLB1 in benign and malignant breast changes, as well as their participation in malignant
transformation.
The research included the analysis of tissue material of benign and malignant changes
in patients operated at the University Clinical Center Kragujevac. All macro and
micromorphological prognostic factors (histological type and grade of tumor, size, nodal
status, desmoplasia, necrosis, mononuclear reaction, etc.) were defined on H&E stained
preparations. Immunohistochemically, using antibodies (p16, p53, p21, pRb, GLB1) tissue
expression of markers were determined by a semiquantitative reading o...f a positive reaction.
By defining cut-off values, cancers were classified into positive and negative groups for each
analyzed marker.
The expression of all markers increased with the progression of cytological changes in
the epithelium. Their expression positively correlated with various changes in the breast, with
the proliferative index and HER2+ tumors. The expression of p16, pRb, p21, GLB1 is the
highest in HER2+ breast cancers, while the expression of p53 is the highest in TNBC. A
significant correlation was found between the expression of p16 and p53, p21 and pRb, p21
and GLB1, as well as between pRb and GLB1 in invasive cancer.
The analyzed markers play an important role in proliferation, malignant
transformation, as well as in the progression of breast cancer, which recommends them for
further research and possible use for diagnostic, prognostic and predictive purposes.