Povezanost BRAF mutacije, histološkog gradusa i mikrosatelitske nestabilnosti s progresijom papilarnog mikrokarcinoma štitnjače

master's thesis

• Title (english): Correlation between BRAF mutation, histological grade and microsatellite instability with progression of papillary thyroid microcarcinoma
• Author: Viktorija Liber
• Mentor: Fabijan Knežević (mentor)
• Mentor: Vesna Benković (mentor)
• Committee member: Vesna Benković (predsjednik povjerenstva)
• Committee member: Biljana Balen (član povjerenstva)
• Committee member: Goran Kovačević (član povjerenstva)
• Committee member: Renata Šoštarić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2018-02-22, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Papilarni mikrokarcinom štitnjače (PTMC) definira se kao tumor manji od 1 cm koji je građen od resica obloženim atipičnim tireocitima. PTMC većinom ima dobru prognozu, no neki PTMC-ovi pokazuju intraglandularnu diseminaciju, metastaze u regionalnim limfnim čvorovima vrata, a rijetko i udaljene metastaze. Cilj ovog istraživanja bio je ustanoviti postoji li povezanost proliferacijskog indeksa Ki-67 (histološki gradus), mikrosatelitske nestabilnosti (MSI), i mutacije BRAF kod PTMC-a s progresijom tumorske bolesti. Imunohistokemijom se na 41 uzorku biopsija tumora PTMC-a odredilo prisustvo mutacije u proteinu BRAF te postojanje MSI, a ostali podaci su preuzeti iz patohistoloških nalaza arhive Zavoda za patologiju i citologiju KB "Sveti Duh". Svi podaci analizirani su deskriptivnom statistikom i neparametrijskim korelacijskim testom Spearman. Bolesnici stariji od 50 godina imali su izraženiji protein MLH1. Metastaze u limfne čvorove vrata pojavile su se češće kod većih tumora. Kod nižih vrijednosti indeksa Ki-67 tumor je češće pokazivao mikrosatelitsku nestabilnost. Mutacija BRAF češće je detektirana u mlađih bolesnika, kod tumora histološkog gradusa 2 te kod većih tumora. Može se zaključiti da je veličina PTMC-a povezana s mutacijom BRAF, MSI te pojavom metastaza.

Abstract (english)

Papillary thyroid microcarcinoma is defined as tumor measuring less than 1 cm; it consists of papillae which are coated with atypical thyreocytes. PTMC predominantly has a good prognosis, but some cases show intraglandular dissemination, metastasis in regional lymph node and rarely distant metastasis. The aim of this study was to determine whether there is a correlation between the proliferation index Ki-67 (histological grade), microsatellite instability (MSI) and BRAF mutation in PTMC, with progression of tumor disease. Immunohistochemistry was used to determine the presence of BRAF mutated proteins and the existence of MSI in the 41 biopsy samples of the PTMC tumor, rest of the data were taken from the pathohistological findings in the archives of the Department of Pathology and Cytology "Sveti Duh". All data were analyzed by descriptive statistics and nonparametric Spearman correlation test. Patients over the age of 50 had more expressed MLH1 protein. Metastases in lymph nodes appeared more frequently in larger tumors. At lower values of the Ki-67 index the tumor showed microsatellite instability. Most BRAF mutations were detected in younger patients, in patients with histological tumor grade 2 and larger tumors. We can conclude that the size of PTMC is associated with BRAF mutations, MSI and the occurrence of metastasis.

• Keywords: papilarni mikrokarcinom štitnjače; mutacija BRAF; Ki-67 indeks; metastaze; mikrosatelitska nestabilnost
• Keywords (english): papillary thyroid microcarcinoma; BRAF mutation; Ki-67 index; metastasis; microsatellite instability
• Language: croatian
• URN:NBN: urn:nbn:hr:217:594754
• Study programme: Title: Experimental Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2018-03-15 13:10:27