Mutacija V600E gena BRAF i izraženost proteina CPSF2 kao prognostički pokazatelji papilarnoga karcinoma štitnjače

doctoral thesis

• Title (english): BRAF V600E mutation and CPSF2 expression as prognostic markers for papillary thyroid cancer
• Author: Irena Ivković
• Mentor: Drago Prgomet (mentor)
• Committee member: Jadranka Sertić (predsjednik povjerenstva)
• Committee member: Andro Košec (član povjerenstva)
• Committee member: Hrvoje Čupić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2022-12-16, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Otorhinolaryngology
• Universal decimal classification (UDC): 616 - Pathology. Clinical medicine

Abstract

Mnogobrojne studije usmjerene su na utvrđivanje prognostičkih biomarkera koji bi nam pouzdano izdvojili agresivne oblike papilarnog karcinoma štitnjače već u početnom stadiju bolesti i time omogućili bolju strategiju liječenja. Većina studija naglašava veliku varijabilnost u prevalenciji mutacije V600E gena BRAF u PKŠ, a kreće se između 30% i 80%, ovisno o zemljopisnom položaju regije i konzumaciji joda. Jedna od novijih studija navodi da je i smanjena ekspresija gena zaduženog za specifični faktor za cijepanje i poliadenilaciju, podjedinica 2 (CPSF2) povezana s invazivnošću karcinomskih stanica i agresivnim oblikom PKŠ. Cilj je ove retrospektivne studije određivanje prisutnosti mutacije V600E gena BRAF i ekspresije proteina CPSF2 na arhivskom bioptičkom materijalu PKŠ i time definiranja pouzdanih biomarkera za prognozu te progresiju metastaziranja PKŠ koji bilježi značajan i stalan porast incidencije.
Na temelju dobivenih rezultata možemo zaključiti da se prisutna mutacija V600E gena BRAF i niska ekspresija CPSF2 proteina ne mogu smatrati samostalnim prediktivnim čimbenicima za razvoj regionalnih metastaza. Utvrdili smo značajnu povezanost mutacije V600E gena BRAF i okultnih metastaza u klinički negativnom vratu. Rezultati ukazuju na to da CPSF2 skupine intenziteta 2 i manje imaju značajno češće recidive, a skupina s kombinacijom pozitivnog nalaza mutacije V600E gena BRAF i izraženosti CPSF2 proteina <3+ ima značajno kraće preživljenje do recidiva.
Na temelju našeg istraživanja možemo zaključiti da bi određivanje prisustva BRAF mutacije i ekspresije CPSF2 proteina u tumorskim tkivima PKŠ unaprijedilo važeće smjernice i klasifikacijski sustav za procjenu rizika ATA.

Abstract (english)

Numerous studies have focused on identifying prognostic biomarkers that reliably predict aggressive forms of papillary thyroid cancer at the early stages of disease and thus enable better treatment strategy. Most studies underline wide variation in the prevalence of BRAF V600E mutation in papillary thyroid cancer, which varies between 30% and 80% depending on geographic region and iodine consumption. Recent study reported that the loss of cleavage and polyadenylation specificity factor subunit 2 (CPSF2) is associated with increased cellular invasion and aggressive form of papillary thyroid cancer. The aim of this retrospective study was to determine the presence of BRAF V600E mutation and CPSF2 protein expression in papillary thyroid cancer archived specimens, thus defining a reliable biomarker for prognosis and progression of metastatic papillary thyroid cancer, which has recorded a significant and steady increase in the incidence.
Based on the obtained results, we can conclude that the presence of the V600E mutation of the BRAF gene and the low expression of the CPSF2 protein cannot be considered independent predictive factors for the development of regional metastases. We found a significant association between the V600E mutation of the BRAF gene and occult metastases in the clinically negative neck. The results indicate that CPSF2 groups with an expression intensity of 2 and less have significantly more frequent relapses, and the group with a combination of a positive finding of the V600E mutation of the BRAF gene and expression of the CPSF2 protein <3+ has a significantly disease-free survival.
Based on our research, we can conclude that determining the presence of BRAF mutation and CPSF2 protein expression in papillary thyroid cancer would improve the current guidelines and classification system for ATA risk assessment.

• Keywords: mutacija V600E gena BRAF; CPSF2; papilarni karcinom štitnjače; metastaze
• Keywords (english): BRAF V600E mutation; CPSF2; papillary thyroid carcinoma; metastases
• Language: croatian
• URN:NBN: urn:nbn:hr:105:295699
• 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: 75 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-01-30 12:03:36