Tesis

Nilai Diagnostik Pemeriksaan Mutasi BRAF, NRAS, dan Promoter TERT pada Keganasan Tiroid dari Spesimen Biopsi Aspirasi Jarum Halus (BAJAH) = Diagnostic Value of BRAF, NRAS and TERT Promoter Mutation in Thyroid Carcinoma from Fine Needle Aspiration Biopsy (FNAB) Specimen.

Latar Belakang: Kanker tiroid merupakan keganasan endokrin yang paling sering ditemukan dan insidennya semakin meningkat. Meskipun metode biopsi aspirasi jarum halus memiliki sensitivitas yang baik dalam mendiagnosis nodul tiroid, sebanyak 10-40% masih memberikan hasil inkonklusif dalam penentuan keganasan. Hal ini sering merugikan pasien karena harus mengalami re-operasi apabila terdapat keganasan pada hasil histopatologi. Tujuan Penelitian: Mengetahui proporsi dan mendapatkan nilai diagnostik dari pemeriksaan mutasi BRAF, NRAS, dan promoter TERT pada spesimen BAJAH untuk meningkatkan akurasi diagnosis kanker tiroid. Metode Penelitian: Studi retrospektif dengan mengikutsertakan 50 pasien nodul tiroid yang memerlukan pembedahan. Spesimen diambil pada saat proses BAJAH atau pasca operasi. Deteksi mutasi BRAF, NRAS, dan promoter TERT menggunakan metode DNA sekuensing (Sanger). Hasil mutasi akan dibandingkan dengan pemeriksaan baku emas histopatologi. Hasil: Dari 50 kasus yang ikut dalam analisis, terdapat 39 kasus (78%) merupakan keganasan tiroid. Nilai proporsi mutasi BRAF, NRAS, dan pTERT berturut-turut sebesar 31%, 18%, dan 13%. Uji diagnostik mutasi BRAF menghasilkan sensitivitas, spesifisitas, nilai duga positif, dan nilai duga negatif berturut-turut 31%, 100%, 100%, 29% terhadap kanker tiroid. Untuk mutasi NRAS sebesar 18%, 100%. 100%, 26%. Sedangkan untuk mutasi pTERT sebesar 13%, 100%, 100%, 24%. Jika ketiga mutasi tersebut dikombinasikan, maka nilainya akan meningkat menjadi 49%, 100%, 100%, 35%. Kesimpulan: Pemeriksaan mutasi BRAF, NRAS dan promoter TERT pada kanker tiroid masing-masing memiliki spesifisitas yang tinggi. Jika ketiganya dikombinasikan maka akan meningkatkan sensitivitas untuk membantu dalam meningkatkan akurasi diagnosis keganasan tiroid.
Kata Kunci: kanker tiroid, mutasi, BRAF, NRAS, promoter TERT, BAJAH, nilai diagnostik



Background: Thyroid cancer is the most common endocrine malignancy and it’s incidence is on the rise. Although the fine needle aspiration biopsy (FNAB) has a good sensitivity in the diagnosis of thyroid nodules, as much as 10-40% still gives inconclusive results in malignant determination. This is often detrimental to patients having to undergo re-surgery if there is a malignancy in the histopathologic outcome. Aim: To establish the proportion and diagnostic value of BRAF, NRAS, and TERT promoter mutation detection on FNAB specimens to improve the accuracy of thyroid cancer diagnosis. Methods: The retrospective study by involving 50 patients with thyroid nodules surgery. Specimens were taken during the FNAB or postoperative process. Detection of BRAF, NRAS, and TERT promoter mutation using DNA sequencing method (Sanger). The mutation results will be compared with the histopathologic gold standard examination. Resuts: Of the 50 cases involved in the analysis, there were 39 cases (78%) of thyroid malignancies. The proportion of BRAF, NRAS, and pTERT mutations was 31%, 18%, and 13%, respectively. BRAF mutation diagnostic test results in sensitivity, specificity, positive predictive value, and negative predictive value were 31%, 100%, 100%, 29% respectively. For NRAS mutation were 18%, 100%. 100%, 26%. As for pTERT mutation were 13%, 100%, 100%, 24%. If the three mutations are combined, then the value will increase to 45%, 100%, 100%, 35%. Conclusion: Detection mutations of BRAF, NRAS and TERT promoters in thyroid cancer have a high specificity. If all three are combined it will increase the sensitivity to improve the accuracy of the diagnosis in thyroid malignancy.
Key words: Thyroid cancer, mutation, BRAF, NRAS, TERT promoter, fine needle aspiration biopsy, diagnostic value