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Agnes Stephanie Harahap,1â 3 Imam Subekti,4 Sonar Soni Panigoro,5 Asmarinah,6 Lisnawati,1 Retno Asti Werdhani,7 Hasrayati Agustina,8 Dina Khoirunnisa,1 Mutiah Mutmainnah,1 Salinah,1 Alvita Dewi Siswoyo,9 Maria Francisca Ham1,2 1Department of Anatomical Pathology, Faculty of Medicine Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia; 2Human Cancer Research Center-Indonesian Medical Education and Research Institute, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia; 3Doctoral Program in Medical Sciences, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia; 4Department of Internal Medicine, Faculty of Medicine Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia; 5Department of Surgery, Faculty of Medicine Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia; 6Department of Medical Biology, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia; 7Department of Community Medicine, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia; 8Department of Anatomical Pathology, Faculty of Medicine Universitas Padjadjaran/Hasan Sadikin General Hospital, Bandung, Indonesia; 9Department of Radiology, Faculty of Medicine Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital, Jakarta, IndonesiaCorrespondence: Agnes Stephanie Harahap, Department of Anatomical Pathology, Faculty of Medicine Universitas Indonesia, Jl. Salemba Raya No. 6, Jakarta, 14320, Indonesia, Tel +62818765563, Email agnes.stephanie01@ui.ac.idIntroduction: BRAFV600E and RAS mutations are the most common gene mutations in papillary thyroid carcinoma (PTC) that may be correlated with its biological behavior. There are still limited data about BRAFV600E and RAS mutations in Indonesia. This study aims to determine the prevalence of BRAFV600E and RAS mutations, and their association with clinicopathologic characteristics.Methods: Patients who had total thyroidectomy from 2019 to 2021 and those who met our study criteria underwent PCR and DNA sequencing analysis for BRAFV600E, BRAFK601E, exon 2 and 3 of NRAS, HRAS, and KRAS. Analyses were performed to determine the associations of BRAFV600E and RAS mutations with clinicopathologic characteristics.Results: Of 172 PTC patients, BRAFV600E mutation was observed in 37.8% of the patients and RAS mutations were found in 21.5%. One patient harbored BRAFK601E mutation. There was a significant association of BRAFV600E with a high-stage (p = 0.033, OR: 3.279; 95% CI: 1.048â 10.259), tall-cell variants (p ⤠0.001, OR: 41.143; 95% CI: 11.979â 141.308), non-encapsulated (p = 0.001, OR: 4.176; 95% CI: 2.008â 8.685), lymphovascular invasion (p = 0.043, OR: 1.912; 95% CI: 1.018â 3.592), extrathyroidal extension (p = < 0.001, OR: 3.983; 95% CI: 1.970â 8.054), and lymph node metastasis (p = 0.009, OR: 2.301; 95% CI: 1.224â 4.326). Follicular variant (p = 0.001, OR: 7.011; 95% CI: 2.690â 18.268), encapsulated (p = 0.017, OR: 2.433; 95% CI: 1.161â 5.100), and absent of extrathyroidal extension (p = 0.033, OR: 2.890; 95% CI: 1.052â 7.940) were associated with RAS mutations.Conclusion: A significant association between BRAFV600E mutation and high clinical stage, tall-cell variants, non-encapsulated morphology, lymphovascular invasion, extrathyroidal extension, and lymph node metastasis in PTC was observed. RAS mutations were associated with the follicular variant, encapsulated tumor, and no extrathyroidal extension. HRAS-mutated PTC frequently exhibited tumor multifocality.Keywords: papillary thyroid carcinoma, BRAFV600E, BRAFK601E, RAS, clinicopathological characteristics |
