Izraženost i prognostičko značenje PD-L1 i NY-ESO1 u karcinomima žučnog mjehura

doctoral thesis

• Title (english): Expression and prognostic significance of PD-L1 and NY-ES01 in gallbladder carcinoms
• Author: Amir Ibukić
• Mentor: Mario Zovak (mentor)
• Mentor: Alma Demirović (komentor)
• Committee member: Božo Krušlin (predsjednik povjerenstva)
• Committee member: Jasna Radić (član povjerenstva)
• Committee member: Tomislav Meštrović (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pathology); Zagreb
• Defense date and country: 2024-10-24, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pathology
• Universal decimal classification (UDC): 616 - Pathology. Clinical medicine

Abstract

Cilj. Karcinom žučnog mjehura je rijetka zloćudna bolest s vrlo visokom smrtnošću, obično zbog dijagnosticiranja u uznapredovalom stadiju bolesti. Cilj ovog istraživanja bio je procijeniti izraženost NY-ESO1 i PD-L1 i njihov utjecaj na prognozu bolesnika s karcinomom žučnog mjehura.
Materijali i metode. Imunohistokemijskim bojenjem odredili smo izraženost NY-ESO1 u tumoru i PD-L1 u tumorskim i intratumorskim imunološkim stanicama u 57 bolesnika s karcinomom žučnog mjehura.
Rezultati. Karcinomi žučnog mjehura izražavaju NY-ESO1 u 68,4 % slučajeva. PD-L1 je izražen u 45,6 % slučajeva, većinom u intratumorskim imunološkim stanicama (35,1%) a rjeđe u tumorskim stanicama (10,5 %). Izraženost NY-ESO1 je u negativnoj korelaciji s izraženošću PD-L1 u imunološkim stanicama (rs = - 0,313; p = 0,021). NY-ESO1 nije pokazao povezanost s bilo kojim kliničko-patološkim parametrom ili ukupnim doživljenjem. Izraženost PD-L1 u imunološkim stanicama bila je značajno viša u tumorima s perineuralnom invazijom (rs = 0,318; p = 0,018) i višim kliničkim stadijem bolesti (rs = 0,339; p = 0,013), ali nije pokazala povezanost s ukupnim doživljenjem. U našem istraživanju, medijan ukupnog doživljenja bolesnika s karcinomom žučnog mjehura je 7 mjeseci, sa stopom petogodišnjeg doživljenja od 10 %. Petogodišnje doživljenje od 42 % postignuto je jedino u bolesnika s karcinomom kliničkog stadija I. Rizik od smrti unutar 12 mjeseci je 5,15 puta veći u slučaju veće dubine invazije tumora (pT 3/4). Također je rizik 2,5 puta veći za bolest dijagnosticiranu u kliničkim stadijima višim od stadija I te dvostuko veći u slučaju višeg histološkog gradusa tumora.
Zaključak. Ovim istraživanjem nije dokazana povezanost PD-L1 i NY-ESO1 s prognozom bolesti. Značajan postotak karcinoma imao je izražene istraživane proteine, stoga bi, prema dosadašnjim spoznajama iz drugih studija, mogli biti mete za ciljanu imunoterapiju. U tom smjeru svakako su potrebna dodatna istraživanja na većem broju uzoraka karcinoma žučnog mjehura.

Abstract (english)

Aim. Gallbladder cancer is a rare malignancy with a very high mortality, usually due to diagnosis in an advanced stage of the disease. Therefore, the aim of this study was to evaluate the clinical significance of NY-ESO1 and PD-L1 and their impact on the prognosis of patients with gallbladder cancers.
Materials and methods. Using immunohistochemical staining, we determined the expression of NY-ESO1 in tumor and PD-L1 in both tumor and intratumoral immune cells in 57 patients with gallbladder cancer.
Results. Gallbladder cancers express NY-ESO1 in 68.4 % of cases. PD-L1 was expressed in 45.6 % of cases, mostly in intratumoral immune cells (35 %) and less often in tumor cells (10.5 %). The expression of NY-ESO1 is negatively correlated with the expression of PD-L1 in immune cells (rs = - 0.313; p = 0.021). NY-ESO1 did not show association with any clinicopathological parameters or overall survival. PD-L1 expression in immune cells was significantly higher in tumors with perineural invasion (rs = 0.318; p = 0.018) and higher clinical stage of disease (rs = 0.339; p = 0.013), but did not show an association with overall survival. In our study, the median overall survival of patients with gallbladder cancer was 7 months, with a 5-year survival rate of 10 %. Five-year survival of 42% was achieved only for patients with clinical stage I cancer. The risk of death within 12 months is 5.15 times higher in case of deeper tumor invasion (pT 3/4); 2.5 times higher for the disease diagnosed in clinical stages higher than stage I and twice higher in the case of a higher histological tumor grade.
Conclusion. This study did not prove a correlation between PD-L1 and NY-ESO1 with the prognosis of gallbladder cancer. A significant percentage of cancers expressed investigated proteins, which, according to previous findings from other studies, could be candidates for targeted immunotherapy. In this direction, additional research on gallbladder cancer is needed.

• Keywords: doživljenje; karcinom žučnog mjehura; NY-ESO1; PD-L1; prognoza
• Keywords (english): Gallbladder cancer; NY-ESO1; PD-L1; overall survival; prognosis
• Language: croatian
• URN:NBN: urn:nbn:hr:105:586709
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 86 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-11-28 10:08:13