Ekspresija gena za protein visoke pokretljivosti 2 skupine A (HMGA2) u diferenciranim karcinomima i benignim bolestima štitnjače [High-mobility group A protein 2 (HMGA2) gene expression in differentiated carcinoma and benign thyroid diseases]

Dabelić, Nina (2016) Ekspresija gena za protein visoke pokretljivosti 2 skupine A (HMGA2) u diferenciranim karcinomima i benignim bolestima štitnjače [High-mobility group A protein 2 (HMGA2) gene expression in differentiated carcinoma and benign thyroid diseases]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

The identification of molecular markers allowing to differentiate between benign and malignant thyroid tumors, or aggressive types of differentiated thyroid cancer (DTC) from those with indolent clinical course, remains a challenge. HMGA2 has oncogenic potential. Correlation between upregulation of HMGA2 gene or protein expression and disease aggressiveness has been proven in several malignant neoplasms, but not in DTC. Aim of this research was to determine HMGA2 gene expression levels by qRT-PCR in tissue samples from patients with different clinical stages of DTC, with thyroid follicular adenoma (FA), and in non-neoplastic thyroid disease, namely nodular goiter (NG). By retrospective analyses of 222 tissue samples (113 DTC, 55 FA, 54 NG), it was determined with high sensitivity and specificity that HMGA2 overexpression predicts DTC or FA. Statistically significantly higher HMGA2 gene expression was found in clinically more advanced stages of DTCs, and was highest in patients with distant metastases, and lowest in DTCs limited to thyroid. Higher levels of HMGA2 gene expression were linked to more aggressive types of DTC (with larger tumor size, higher T-stage, multicentricity, extracapsular extension, limfovascular invasion and invasion beyond thyroid, higher pN-stage, larger number of lymphonodal metastases, and lymph node capsule penetration), and to worse clinical responses and outcomes (higher ATA-risk-stratification group, worse ATA-clinical outcome of therapy, non-avidity for radioiodine, higher risk of locoregional recurrence, and higher risk of death from DTC). HMGA2 possibly has a role in DTC carcinogenesis.

Abstract in Croatian

Identificiranje molekularnih biljega za razlikovanje benignih od malignih novotvorina štitnjače, te agresivnijih oblika diferenciranih karcinoma štitnjače (DKŠ) od onih indolentnog kliničkog tijeka, ostaje veliki izazov. HMGA2 ima onkogeni potencijal. Povezanost povećane ekspresije gena ili proteina HMGA2 s agresivnom bolešću dokazana je kod više različitih zloćudnih novotvorina, no ne i kod diferenciranih karcinoma štitnjače. Cilj je ovoga istraţivanja utvrditi razine ekspresije gena HMGA2 metodom qRT-PCR u tkivima bolesnika s različitog kliničkom uznapredovalošću diferenciranih karcinoma štitnjače, folikularnim adenomima (FA) štitnjače i neneoplastičnim bolestima štitnjače - nodoznim strumama (NS). Retrospektivnom analizom iz 222 uzorka primarnog tumora (113 DKŠ, 55 FA, 54 NS), utvrĎeno je da ekspresija gena HMGA2 s velikom osjetljivošću i specifičnošću predviĎa je li riječ o DKŠ ili FA. Veća ekspresija gena HMGA2 povezana je s agresivnijim oblicima DKŠ (većim promjerom primarnog tumora, većim T-stadijem bolesti, multicentričnošću, ekstrakapsularnom ekstenzijom, prisutnošću limfovaskularne invazije i invazije u okolinu, većim pN-stadijem, većim brojem zahvaćenih limfnih čvorova i probojem njihove kapsule), te s lošijim kliničkim odgovorima i ishodima liječenja (većom rizičnom skupinom prema ATA-sustavu stratifikacije rizika i prema ATA-kliničkom ishodu liječenja, neavidnošću na radiojod, većim rizikom od lokoregionalnog recidiva i većim rizikom smrti od DKŠ). HMGA2 moţda ima ulogu u karcinogenezi DKŠ.

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