Title Imunohistokemijska razina EGF-a, EGFR-a i HIF-1ɑ u posteljicama iz trudnoća kompliciranih preeklampsijom
Title (english) Immunohistochemical levels of EGF, EGFR and HIF-1ɑ in placentas from pregnancies complicated by preeclampsia
Author Indira Kosović
Mentor Sandra Zekić Tomaš (mentor)
Committee member Damir Roje (predsjednik povjerenstva)
Committee member Snježana Tomić (član povjerenstva)
Committee member Slavko Orešković (član povjerenstva)
Granter University of Split School of Medicine Split
Defense date and country 2022-01-13, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Clinical Medical Sciences Gynecology and Obstetrics
Universal decimal classification (UDC ) 618 - Gynaecology. Obstetrics
Abstract Cilj: Istražiti imunohistokemijski izražaj faktora rasta EGF-a, EGFR-a, transkripcijskog faktora
HIF-1α u VTB-u, EVTB-u i DS-u terminskih posteljica iz trudnoća s PE-om i terminskih
posteljica urednih trudnoća te rezultate međusobno usporediti. Istražiti proliferacijski indeks u
VTB-u, EVTB-u i u DS-u terminskih posteljica s PE i usporediti sa zdravom kontrolom.
Materijali i metode: Ispitivanu skupinu čini 29 posteljica jednoplodnih trudnoća trećeg
tromjesječja kompliciranih PE i 19 terminskih posteljica iz urednih trudnoća kao kontrolna
skupina. Klinička dijagnoza PE postavljena je na temelju strogih kriterija za arterijsku
hipertenziju u prethodno normotenzivnih žena i proteinurije. Kriteriji isključenja obuhvaćali su
prethodno postojanje arterijske hipertenzije, bolesti bubrega te vaskularne bolesti i
dijagnosticiran HELLP sindrom. Izražaj EGF-a, EGFR-a i HIF-1α određivan je
imunohistokemijskom metodom upotrebom specifičnih protutijela. Proliferacijska aktivnost
određivana je zasebno za DS, EVT i EVTB koristeći antigen Ki-67. Imunohistokemijsko
bojanje protutijelom CK7 omogućilo je razlikovanje DS-a od EVTB-a.
Rezultati: Nije pronađena statistički značajna razlika u imunohistokemijskom izražaju EGF-a i
EGFR-a između terminskih posteljica s PE i terminskih urednih posteljica kontrolne skupine.
Imunohistokemijski izražaj HIF-1α statistički je značajno viši kod terminskih posteljica s PE u
odnosu na uredne terminske posteljice kontrolne skupine. Proliferacijski indeks znatno je viši
u DS-u i EVTB-u kod posteljica iz trudnoća s PE u usporedbi s urednim terminskim
posteljicama kontrolne skupine. Iako je proliferacijski indeks bio viši u DS-u u odnosu na
EVTB kod obje skupine, ta se razlika nije pokazala statistički značajnom.
Zaključak: Imunohistokemijski izražaj faktora rasta EGF-a i receptora za EGF nije se
razlikovao između posteljica sa PE i kontrolnih terminskih posteljica zbog mogućeg gubitka
uloge ovog faktora rasta pred kraj trudnoće. Budući postoje četiri receptora te četrnaest liganda
i barem tri signalna puta preko kojih navedeni ostvaruju svoje djelovanje, moguće je da baš
drugi ligandi poput HB-EGF-a više utječu na pojavnost PE u terminskim posteljicama.
Imunohistokemijski izražaj transkripcijskog faktora rasta HIF-1α pokazao se višim u svim
segmentima posteljica s PE u odnosu na posteljice kontrolne skupine. Ispitujući
imunohistokemijski izražaj HIF-1α faktora u DS-u, dokazali smo da i majčin dio posteljice
iskazuje isti odgovor na hipoksiju kao i fetalni. Kako i upalni citokini, autoantitijela koja su
povišena u PE, mogu neovisno o hipoksiji dovoditi do povišenog izražaja HIF-1α, u
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obrazloženju rezultata studije treba razmišljati i o navedenim parakrinim utjecajima. Rana
ubrzana proliferacija DS-a i EVTB-a nužna je za pravilan rast i razvoj posteljice. Gotovo tri
puta viši proliferacijski indeks u DS-u i EVTB-u posteljica s PE u odnosu na kontrolne
terminske posteljice moguće predstavlja kompenzatorni mehanizam, kao posljedicu
neadekvatne proliferacije i diferencijacije u ranim stadijima trudnoće.
Abstract (english) Purpose: To examine the immunohistochemical expression of the EGF growth factor, the
transcription factor of HIF-1α in the VTB, EVTB and DS of term placentae from PE
pregnancies and term placentae from orderly pregnancies, and to compare the results. To
examine the proliferation index in the VTB, EVTB and DS of PE term placentae and to compare
them to a healthy control group.
Materials and methods: The examined group consists of 29 placentae from third trimester
singleton pregnancies with a complicated PE and 19 term placentae from orderly pregnancies
as a control group. The PE clinical diagnosis was set based on strict criteria for arterial
hypertension in previously normotensive women and proteinuria. The exclusion criteria
included the prior existence of arterial hypertension, kidney disease, as well as vascular disease
and a diagnosed HELLP syndrome. The EGF, EGFR and HIF-1α expression was determined
by the immunohistochemical method through the usage of specific antibodies. The proliferation
activity was determined separately for DS, EVT and EVTB through the use of the Ki-67
antigen. The immunohistochemical staining with the CK7 antibody enabled the differentiation
between DS and EVTB.
Results: No statistically significant difference in the immunohistochemical expression of the
EGF and EGFR was found between the PE term placentae and orderly term placentae of the
control group. The HIF-1α immunohistochemical expression is statistically significantly higher
in PE term placentae in relation to the orderly term placentae of the control group. The
proliferation index is significantly higher in DS and EVTB in placentae from PE pregnancies
in relation to the orderly term placentae of the control group. Although the proliferation index
was higher in DS in relation to EVTB in both groups, that difference did not prove to be
statistically significant.
Conclusion: The immunohistochemical expression of the EGF growth factor and the EGF
receptor did not differ between the PE placentae and the control term placentae due to the
possible loss of role of this growth factor towards the end of the pregnancy. Because there are
four receptors and fourteen ligands, and at least three signal pathways through which the
aforementioned perform their activity, it is possible that precisely other ligands, such as
HBEGF, affect the incidence of PE in term placentae more.
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The immunohistochemical expression of the HIF-1α transcription growth factor was higher in
all segments of the PE placentae compared to the control group placentae. By examining the
immunohistochemical expression of the HIF-1α factor in DS, we have proven that the mother’s
portion of the placenta exhibits the same response to hypoxia as the fetal does. As the
inflammatory cytokines, antibodies that are high in PE can lead to a higher expression of HIF1α independently from hypoxia, the explanation of the study results has to take into
consideration the listed paracrine influences as well. An early accelerated proliferation of DS
and EVTB is necessary for the proper growth and development of the placenta. The nearly triple
proliferation index in DS and EVTB of PE placentae in relation to the control term placentae
might represent a compensatory mechanism as a consequence of inadequate proliferation and
differentiation in the early stages of the pregnancy.
Keywords
preeklampsija
intrauterini zastoj rasta
EGF
EGFR
HIF-1α
Keywords (english)
Rad ne sadrži ključne riječi na drugom jeziku.
Language croatian
URN:NBN urn:nbn:hr:171:913449
Promotion 2022
Study programme Title: Obtaining a doctorate of science outside of doctoral studies Study programme type: university Study level: postgraduate Academic / professional title: doktor/doktorica znanosti (doktor/doktorica znanosti)
Type of resource Text
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Created on 2022-01-24 14:10:56