Title Povezanost izraženosti E-kadherina i učinkovitosti prvolinijske kemoterapije kod seroznog karcinoma jajnika Title (english) Correlation between E-cadherin expression and the effectiveness of first-line chemotherapy in serous ovarian cancer Author Branka Petrić Miše Mentor Eduard Vrdoljak (mentor)Committee member Katarina Vilović (predsjednik povjerenstva)Committee member Antonio Juretić (član povjerenstva)Committee member Tomislav Strinić (član povjerenstva)Granter University of Split Defense date and country 2014, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 616 - Pathology. Clinical medicine Abstract Cilj ovog istraživanja bio je analizirati povezanost imunohistokemijske izraženosti E-kadherina
i učinkovitosti prvolinijske kemoterapije temeljene na spojevima platine kod
bolesnica s uznapredovalim stadijem slabo diferenciranog seroznog karcinoma jajnika.
Izraženost E-kadherina je analizirana imunohistokemijski na parafinskim tumorskim
blokovima od 98 bolesnica s uznapredovalim stadijem slabo diferenciranog seroznog
karcinoma jajnika i potom istraživana povezanost s kliničkim značajkama (stadij bolesti
definiran prema Međunarodnoj federaciji za ginekologiju i opstetriciju (FIGO) i ostatna
bolest nakon primarne citoredukcije), s odgovorom na kemoterapiju temeljenu na
spojevima platine (definiran prema RECIST 1.1 kriterijima), s kemoosjetljivošću
(definiranu prema platina slobodnom intervalu) te s preživljenjem do progresije bolesti
(PFS) i ukupnim preživljenjem (OS).
Imunohistokemijska izraženost E-kadherina bila je pozitivna u 74 uzorka, i negativna u
24 uzorka seroznog karcinoma jajnika. Izraženost E-kadherina nije bila povezana s
FIGO stadijem, ostatnim tumorom nakon primarne citoredukcije i brojem ciklusa
kemoterapije. Pozitivna izraženost E-kadherina je statistički značajno povezana s
boljim odgovorom na prvolinijsku kemoterapiju temeljenu na spojevima platine
(P<0.001) i s kemoosjetljivosti na spojeve platine (P<0.001). Osim toga, pozitivna
izraženost E-kadherina je povezana s dužim preživljenjem do progresije bolesti
(P<0.001) i ukupnim preživljenjem (P<0.001). Multinominalna analiza za ukupno
preživljenje je pokazala da pozitivna izraženost E-kadherina jest nezavisni
predskazatelj kemoosjetljivosti na spojeve platine (P<0.001) i dužeg ukupnog
preživljenja (P=0.01).
Rezultati ovog istraživanja su ukazali da je pozitivna izraženost E-kadherina
predskazatelj boljeg odgovora na prvolinijsku kemoterapiju temeljenu na spojevima
platine, bolje kemoosjetljivosti na spojeve platine i povoljnijeg kliničkog ishoda kod
bolesnica s uznapredovalim stadijem slabo diferenciranog seroznog karcinoma jajnika.
Negativna izraženost E-kadherina predstavlja značajan neovisni predskazatelj lošijeg
preživljenja do progresije bolesti i ukupnog preživljenja. Vrlo je vjerojatno da Ekadherin
kao biljeg uz prognostičku ima i prediktivnu vrijednost. Temeljem izraženosti
E-kadherina bolesnice s uznapredovalim slabo diferenciranim seroznim karcinomom
jajnika mogle bi se probirati glede prvolinijske kemoterapije, te bi se inicijalno
refraktorne bolesnice mogle poštedjeti toksične i neučinkovite sistemne terapije. Uz potencijalnu farmakoekonomsku uštedu za društvo, ovi rezultati otvaraju vrata ciljane
onkološke terapije koja bi bila usmjerena na najvažnije karike epitelno-mezenhimalne
preobrazbe, ali isto tako predstavljaju poticaj za daljna istraživanja u patogenezi
karcinoma jajnika.
Abstract (english) The purpose of our study was to analyze correlation between immunoexpression of Ecadherin
and efficacy of first line platinum-based chemotherapy in patients with
advanced-stage, high-grade serous ovarian carcinoma.
The expression of E-cadherin was analyzed immunohistochemically in formalin-fixed,
paraffin-embedded samples from 98 patients with advanced-stage, high-grade serous
ovarian cancer and related to clinical features (stage according to the International
Federation of Gynecology and Obstetrics (FIGO) and residual tumors after initial
cytoreductive surgery), response to platinum-based chemotherapy (according to
Response Evaluation Criteria in Solid tumors (RECIST 1.1 criteria)), platinum
sensitivity (according to platinum free interval (PFI) as platinum-refractory, platinumresistant
and platinum-sensitive) and patients progression free survival (PFS) and
overall survival (OS).
E-cadherin immunostaining was positive in 74 and negative in 24 serous ovarian
carcinomas. E-cadherin immunoreactivity was not associated with FIGO stage, residual
tumor after initial cytoreductive surgery and number of chemotherapy cycles. Positive
E-cadherin expression predicts significantly better response to first line platinum-based
chemotherapy (P<0.001) and platinum sensitivity (P<0.001). Moreover, positive Ecadherin
expression predicts significantly longer PFS (P<0.001) and OS (P<0.001).
The multivariate analysis for OS showed that positive E-cadherin expression is
predictor to platinum sensitivity (P<0.001) and longer OS (P=0.01).
Positive E-cadherin expression seems to be a predictor of better response to first line
platinum-based chemotherapy, platinum sensitivity and favorable clinical outcome in
patients with advanced-stage serous ovarian cancer. Negative E-cadherin expression
was shown to be significant, independent predictor of poorer PFS and OS. E-cadherin
as a marker has predictive and prognostic value. Based on E-cadherin expression,
patients with advanced poorly differentiated serous ovarian cancer could be screened
with regard to first-line chemotherapy, and all of these with initially refractory tumours
could be spared from the toxic and ineffective systemic therapy. Except potentially
farmoeconomic savings for society, these results open the door to targeted oncology
therapies that would aim at the most important links in the epithelial-mesenchymal transformation but also represent a stimulus for further research into the pathogenesis
of ovarian cancer.
Keywords
Novotvorine jajnika
Kadherini
Keywords (english)
Ovarian Neoplasms
Cadherins
Language croatian URN:NBN urn:nbn:hr:171:152022 Study programme Title: Obtaining a doctorate of science outside of doctoral studies Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2023-06-02 10:04:31
