Title Izražaj lipokalina-2 i matriks metaloproteinaze-9 u karcinomu endometrija visokoga gradusa i njihov prognostički značaj Title (english) Expression of lipocalin-2 and matrix metalloproteinase-9 in high-grade endometrial carcinoma and their prognostic significance Author Sanja Srdelić Mihalj Mentor Ivana Kuzmić Prusac (mentor)Committee member Tomislav Strinić (predsjednik povjerenstva)Committee member Eduard Vrdoljak (član povjerenstva)Committee member Snježana Tomić (član povjerenstva)Granter University of Split Defense date and country 2018, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 618 - Gynaecology. Obstetrics Abstract Karcinom endometrija najčešća je zloćudna novotvorina ženskoga spolnog sustava u razvijenim zemljama i obuhvaća gotovo 50% svih ginekoloških karcinoma. Iako je to bolest s dobrom prognozom i sveukupno visokim preživljenjem, dio pacijentica je u grupi visokog rizika za povrat bolesti i nepovoljni ishod. Grupa visokog rizika, u koju se ubrajaju serozni, svijetlostanični i endometrioidni karcinom endometrija gradusa 3, obuhvaća tek oko 20 − 30% svih karcinoma endometrija, ali u sveukupnoj smrtnosti od ovog karcinoma sudjeluje s 80%. Kad se u grupi visokog rizika dogodi povrat bolesti, odgovor na sistemnu terapiju je ograničen i preživljenje nisko. Velik broj molekularnih markera u dosadašnjim je istraživanjima analiziran da se razjasni karcinogeneza endometralnih karcinoma i odrede molekularni putevi koji sudjeluju u karcinogenezi, progresiji i metastaziranju bolesti. U ovome radu promatran je izražaj proteina LCN-2 i MMP-9. Oba su spomenuta markera široko istraživana u biologiji tumora, posebice lipokalin-2. U karcinomu endometrija postoje tek tri rada koji proučavaju LCN-2, i nekoliko radova koji istražuju MMP-9. Radovi koji istražuju zajednički izražaj lipokalina-2 i matriks metaloproteinaze-9 do sada nisu rađeni. Imunohistokemijskom metodom, na tkivu karcinoma endometrija uklopljenom u parafinske kocke, odredio se izražaj lipokalina-2 i matriks metaloproteinaze-9. Pokazalo se da su i lipokalin-2 i matriks metaloproteinaza-9 prisutni u 69,4%, odnosno 67,6%, a jako izraženi u 30,5 % odnosno 30,6 % karcinoma endometrija visokoga gradusa te da njihova izraženost korelira s lošijim preživljenjem (sa sveukupnim preživljenjem i preživljenjem bez bolesti). Također, podgrupa pacijentica s pozitivnim i LCN-2 i MMP-9 izražajem imala je lošije preživljenje nego one koje su imale pozitivan izražaj samo LCN-2 ili MMP-9 ili ni jedno ni drugo. Univarijantna analiza pokazala je da i LCN-2 i MMP-9 imaju utjecaj na preživljenje, dok se u multivarijantnoj analizi pokazalo da je LCN-2 nezavisni prognostički čimbenik lošije prognoze bolesti. Prognostička vrijednost ovih dvaju biomarkera je promatrana odvojeno u endometrioidnom karcinomu visokoga gradusa i u seroznom karcinomu. Pokazalo se da prognostička vrijednost postoji i u endometrioidnom karcinomu visokoga gradusa i u seroznom karcinomu. Univarijantna analiza u endometrioidnom karcinomu visokoga gradusa pokazala je da postoji povezanost između jakog LCN-2 izražaja i kraćeg DFS-a i OS-a, dok je za jaki MMP-9 izražaj dokazana korelacija samo s kraćim DFS-om. Mutivarijantna analiza pokazala je da je samo jaki LCN-2 izražaj povezan s kraćim DFS-om i OS-om, a da ne postoji takva povezanost s MMP-9 izražajem. U seroznom karcinomu, univarijantna analiza pokazala je povezanost jakog LCN-2 i MMP-9 izražaja s kraćim DFS-om i OS-om, dok je multivarijantnom analizom dokazano da je samo jaki LCN-2 izražaj povezan s kraćim DFS-om i OS-om.
Abstract (english) Endometrial cancer is the most common malignant neoplasm of the female genital tract in developed countries and covers almost 50% of all gynecological cancers. Although it is a disease with a good prognosis and overall survival, the part of the patients is at high risk for recurrence and unfavorable outcome. High-risk group, which include serous, clear cell and endome-trial cancer grade 3, covers about 20-30% of all endometrial cancer, but the overall mortality from this cancer accounts for 80%. When relapse occurs in a group of high risk carcinoma, the response to systemic therapy is limited and survival is law. A large number of molecular markers has been analyzed in order to clarify the carcinogenesis of endometrial cancer and to determine the molecular pathways involved in carcinogenesis, progression and -metastasis of the disease. In this paper we studied the immunochistochemical expression of the protein LCN-2 and MMP-9. Both mentioned markers has been widely investigated in tumor biology, particularly LCN-2. In endometrial cancer, there are only three papers that have studied LCN-2, and several works that have explored the MMP- 9. Works that explored a common expression of LCN-2 and MMP-9 have not yet been done. Immunohistochemical expression was determined on archived paraffin-embedded samples using LCN-2 and MMP-9 antibodies. It was shown that their expressions correlate with poorer survival (with overall and disease-free survival). Also, the subgroup of patients with a positive LCN-2 and MMP-9 co-expression had worse survival than the group that had a positive expression of LCN-2 or MMP-9 separately or neither. Univariate analysis showed that the LCN-2 and MMP-9 had an impact on survival while multivariate analysis showed that LCN-2 was an independent prognostic factor for poor prognosis. The prognostic relevance of these two biomarkers was observed separately in high-grade endometrioid carcinomas and serous carcinomas. Univariate analysis of endometrioid carcinomas grade 3 revealed correlation between strong LCN-2 expression and shorter OS and DFS, while MMP-9 showed correlation with DFS only. On multivariate analysis, only strong LCN-2 expression correlated with shorter DFS and OS, while there was no such association with MMP-9. In serous carcinomas, univariate analysis yielded correlation of both LCN-2 and MMP-9 with reduced survival, both OS and DFS, while on multivariate analysis only LCN-2 expression correlated with poorer OS and DFS. In conclusion, both markers have a prognostic value, comparable to ECG3 and serous carcinoma.
Keywords
Novotvorine endometrija
Lipokalin-2
Matriks metaloproteinaza-9
Keywords (english)
Endometrial Neoplasms
Lipocalin-2
Matrix Metalloproteinase 9
Language croatian URN:NBN urn:nbn:hr:171:749060 Study programme Title: Basic and clinical medical sciences Type of resource Text File origin Born digital Access conditions Open access Terms of use Repository MEFST Repository Created on 2023-05-11 12:30:43
