Clinical Utility of BRAF, NRAS, and TERT Promoter Mutation in Preoperative Thyroid Fine-Needle Aspiration Biopsy: A Diagnostic Study From Dharmais Cancer Hospital

Abstract

Objective: Molecular testing of thyroid nodules becomes important for improving the accuracy of fine-needle aspiration biopsy (FNAB). This study aimed to investigate the diagnostic utility of BRAF, NRAS, and TERT promoter mutation in thyroid nodules at Dharmais Cancer Hospital. Methods: We performed a prospective diagnostic study involving 50 patients with thyroid nodules who needed surgery between September 2013 and August 2014. Mutational hotspots in BRAF exon 15, NRAS exon 3, and TERT promoter region were analyzed by Sanger sequencing from FNAB specimens. Cytology and molecular data were compared to histopathology results. Results: Of the 50 cases included in the analysis, 39 cases (78%) were thyroid malignancies. Mutations of BRAF, NRAS, and TERT promoter were detected in 31% (12/39), 18% (7/39), and 13% (5/39) cases, respectively. BRAF and NRAS mutations were found mutually exclusive, while all of TERT promoter mutation was found coexistent either with BRAF (40%) or NRAS (60%). The combination of FNAB cytology and molecular testing resulted in 69% sensitivity, 100% specificity, 100% positive predictive value, 48% negative predictive value, and 76% accuracy. Conclusion: Molecular testing of BRAF, NRAS, and TERT mutations improve the sensitivity of thyroid FNAB and is beneficial for more definitive treatment in selective cases. However, the NPV is relatively low to avoid the need for diagnostic surgery. Therefore, further studies to identify more sensitive methods and more comprehensive molecular markers in the diagnosis of thyroid nodules are needed.

BRAFV600E mutation test on fine‐needle aspiration specimens of thyroid nodules: Clinical correlations for 4600 patients

“… 36 , 37 The prevalence of BRAF V600E mutation in PTC is 63.6%–83% among Korean and Chinese PTC patients, 38 , 39 , 40 which is much higher than that reported in Western countries (30–72%). 41 , 42 In our study, the frequency of BRAF V600E mutation in PTC was 76.1%. The different prevalence of BRAF V600E mutations among populations may be related to variations in iodine consumption in the diet.…”

Profile of BRAFV600E, BRAFK601E, NRAS, HRAS, and KRAS Mutational Status, and Clinicopathological Characteristics of Papillary Thyroid Carcinoma in Indonesian National Referral Hospital

“…This result is similar to the previous finding from Southeast Asia by Navarro-Locsin et al, 22 which reported the BRAFV600E mutation rate was 38.5%. Similar to our result, there were studies in Indonesia conducted by Heriyanto et al 23 and Perdana AB et al 18 that used molecular methods and reported BRAFV600E mutation rates were 40.3% and 31%, respectively. A single-center cohort study in Singapore reported BRAF mutation in 56% of the PTC patients.…”

“…Yet, most of the studies used immunohistochemistry modality and/or cytology specimens with limited samples. [14][15][16][17][18] Given the dearth of research describing the prevalence of BRAF and RAS mutations in PTC in Indonesia, this study aimed to assess the prevalence of BRAFV600E, BRAFK601E, and RAS (NRAS, HRAS, and KRAS) mutations and their association with the clinicopathological profiles of PTC that were related to the tumor behavior and prognosis in Indonesian population.…”

BRAF V600E Mutation Test in Fine Needle Aspiration (FNA) Specimens of Thyroid Nodules by Competitive Allele-Specific TaqMan PCR (castPCR)

“…Although most thyroid nodules can be accurately identified as benign or malignant, 10%-40% of thyroid nodules are unable to be identified by FNA biopsy [5,6,22,23]. In our previous study, there were 30% of indeterminate results with most of them confirmed histopathologically to be malignant [24]. This means that up to 3 out of 10 patients may have cancer that is not precisely diagnosed, which confirms the high rate of underdiagnosed cases from FNA cytological examination.…”