Značaj poremećaja gena regulatora ćelijskog ciklusa i ekspresije njihovih proteina u rabdomiosarkomu
Significance of disorder of the cell cycle regulator genes and expression of their proteins in rhabdomyosarcoma
Докторанд
Glumac, Sofija Đ.Ментор
Sopta, JelenaЧланови комисије
Vasiljević, JovanBasta-Jovanović, Gordana
Bunjevački, Vera
Radojević-Škodrić, Sanja
Метаподаци
Приказ свих података о дисертацијиСажетак
Cilj: Rabdomiosarkom (RMS) je tumor visokog stepena maligniteta. Poslednje dve decenije
prognoza pacijenata sa ovim tumorom je značajno poboljšana, osim kod pacijenata iz
visokorizične grupe. U cilju utvrđivanja novih prognostičkih faktora ispitivali smo
imunohistohemijsku ekspresiju proteina regulatora ćelijskog ciklusa i apoptoze, kao i obrasce
metilacije promotora gena p16 u slučajevima RMS, i dobijene rezultate korelirati sa kliničkopatološkim
parametrima.
Metodologija: Ova studija je obuhvatila 67 slučajeva RMS dijagnostikovanih na Institutu za
patologiju Medicinskog fakulteta, Univerziteta u Beogradu, u periodu od 1994-2014 godine
Analizirani su sledeći kliničko-morfološki podaci: pol, starost, lokalizacija i veličina tumora,
histološki tip i gradus, zahvaćenost regionalnih limfnih nodusa i postojanje metastatske bo lesti.
Rezultati: Evaluacijom ekspresije ciklina A u odnosu na kliničko-patološke parametre
pacijenata sa RMS, uočena je statistička značajnost samo u odnosu na histo...lški tip tumora
(p=0.047). U ćelijama RMS, ciklin D1 je pokazivao jedarnu ekspresiju i aberantna ekspresija
ovog markera nije pokazivala značajnu korelaciju sa ispitivanim parametrima. Rezultati različite
ekspresija p57 u ovom tumoru su pokazivali statističku značajnost u odnosu na histološki tip
(p=0,042),gradus tumora (p=0,026) i u odnosu na ishod bolesti (p=0,021). Ekspresija survivina u
tumorskim ćelijama RMS bila je citoplazmatska i jedarna, Za razliku od citoplazmatske
ekspresije survivina gde nije uočena njena povezanost sa prognostičkim faktorima, jedarna
ekspresije ovog markera je bila statistički značajna u odnosu na starosne grupe, histološki tip i
gradus tumora (p=0.009, p=0.008, p=0.010, redom). Analiza ekspresije nestina je pokazala
statistički značaj u odnosu na starost pacijeanta (p = 0,028) i gradus tumora (p = 0,022)...
Objective: Rhabdomyosarcoma (RMS) is a tumor of high-grade malignancy. During the last two
decades the prognosis of patients with this tumor has been significantly improved, except in
patients from the high-risk group. In order to determine new prognostic factors, we investigated
the immunohistochemical expression of proteins, the regulators of cell cycles and apoptosis as
well as the patterns of methylation of the p16 gene promoter in cases of RMS, and the results
obtained were to be correlated with clinicopathological parameters.
Methodology: This study included 67 cases of RMS diagnosed at the Institute of Pathology,
School of Medicine, University of Belgrade, in the period from 1994 to 2014. The following
clinical and morphological data were analyzed: gender, age, tumor size and localization,
histological type and grade, affected regional lymph nodes and the presence of metastatic
disease.
Results: By evaluation of the expression of cyclin A in relation to the clinicopathological
p...arameters of patients with RMS, it was found a statistical significance only in relation to the
histological type of tumor (p = 0.047). In the RMS cells, cyclin D1 showed a nuclear expression
and the aberrant expression of this marker did not show any significant correlation with the
studied parameters. Results of different expressions of p57 in this tumor showed a statistical
significance in relation to the histological type (p = 0.042), tumor grade (p = 0.026) and in
relation to the disease outcome (p = 0.021). The survivin expression in RMS tumor cells was
cytoplasmic and nuclear. Unlike cytoplasmic survivin expression where no correlation with
prognostic factors was found out, the nuclear expression of this marker was statistically
significant in relation to the age groups, histological type of tumor and tumor grade (p = 0.009 , p
= 0.008, p = 0.010, respectively).Analysis of the expression of nestin showed statistical
significance in relation to the age of patients (p = 0.028) and tumor grade (p = 0.022)...