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PAPİLLER TİROİD KANSERİ HASTALARINDA BRAF, NRAS, TERT PROMOTER MUTASYON SIKLIĞI VE MUTASYONLARIN KLİNİKOPATOLOJİK ÖZELLİKLER VE UZAK METASTAZ İLE İLİŞKİSİNİN İNCELENMESİ

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tez en son17.03.2022-pdf.pdf (1.128Mb)
tez en son17.03.2022-pdf.pdf (1.128Mb)
tez en son17.03.2022-pdf.pdf (1.128Mb)
tez en son17.03.2022-pdf.pdf (1.128Mb)
tez en son17.03.2022-pdf.pdf (1.128Mb)
tez en son17.03.2022-pdf.pdf (1.128Mb)
Date
2022
Author
Yılmaz, Ezgi
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Abstract
Yılmaz. E., The frequency of BRAFV600E, TERT promoter, NRASmutations in patients with papillary thyroid cancer and the relationship of these mutations with clinicopathological features and distant metastasis, Hacettepe University Faculty of Medicine, Medical Specialty, Thesis in Internal Medicine. Ankara, 2021. Various molecular mechanisms play a role in the pathogenesis of papillary thyroid cancer (PTC). Distant metastasis is a rare condition in PTC and is associated with a poor outcome. Understanding the underlying pathogenesis and molecular changes is needed to improve clinical outcomes in PTC. In this study, we aimed to determine the frequency of BRAFV600E, TERT Promoter and NRAS mutations in patients with papillary thyroid cancer, and the relationship of mutations with clinicopathological features and distant metastasis. Mutations were detected by PCR and direct sequencing method from the paraffin-embedded tumor tissues of 42 PTC patients (16 with distant metastasis and 42 without) over 18 years of age who were followed up in Hacettepe University Hospital and archived in the Department of Pathology between 2004-2021. Pearson’s, chi-square and Mann-Whitney U tests were used for statistical analysis. A P value <0.05 was considered statistically significant. The frequency of BRAFV600E mutation was found to be 64.3%(27/42) in the total group. BRAF positivity was found in 22.2% (6/15) of patients with distant metastasis, and %77.8% (21/25) in those without distant metastasis (p=0.006). There was no statistically significant difference between BRAFV600E mutation and age at diagnosis, gender, tumor size, aggressive histological variant, extrathyroidal invasion, multifocality, lymphovascular invasion, capsule invasion, lymph node metastasis, recurrence and distant metastasis. The frequency of TERT promoter mutation was found to be 9.5%(4/42). These mutations were all at position C228T. No statistically significant difference between TERT promoter mutation and age at diagnosis, gender, tumor size, aggressive histological variant, extrathyroidal invasion, multifocality, lymphovascular invasion, capsule invasion, lymph node metastasis, recurrence and distant metastasis. No NRAS mutation was detected in any of the PTC cases in the study (0/42). There was no statistically significant difference for clinicopathological features and distant metastasis in cases with BRAFV600E and TERT promoter mutations and in cases with both. In conclusion, BRAFV600E mutation was found to be frequent in our PTC cases. Our results indicate that BRAFV600E and TERT promoter mutations, either in isolation or together, do not seem to be prognostic or predictive for distant metastasis in PTC.
URI
http://hdl.handle.net/11655/25997
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