High BRAFV600E mutation frequency in Chinese patients with papillary thyroid carcinoma increases diagnostic efficacy in cytologically indeterminate thyroid nodules

Abstract

To estimate the BRAFV600E mutation frequency in Chinese patients with papillary thyroid carcinoma (PTC), and the diagnostic value of BRAFV600E mutation status in thyroid nodules with indeterminate TBSRTC categories. A total of 4875 consecutive samples for thyroid ultrasound-guided fine-needle aspiration cytology (FNAC) and BRAF V600E mutation analysis were collected from patients at Jiangsu Province Hospital on Integration of Chinese and Western Medicine. Among all the cases, 314 underwent thyroidectomy. According to TBSRTC categories, FNAC was performed for a preoperative diagnosis. ROC of the subject was constructed to evaluate the diagnostic value of these 2 methods and their combination. BRAF V600E mutation in FNAC of thyroid nodules occurred in 2796 samples (57.35%). Of 353 nodule samples from 314 patients with thyroid operation, 333 were pathologically diagnosed as PTC. Of these PTC patients, 292 (87.69%) were found to have BRAF V600E mutation in their preoperative FNAC. In 175 cytologically indeterminate thyroid nodules, BRAF V600E mutation identified 88% of PTC. According to ROC data, BRAF V600E mutation testing had an obviously higher sensitivity (87.69%) and specificity (100.00%) than TBSRTC. Combining BRAF V600E mutation testing and TBSRTC achieved the largest AUC (0.954). For 41 PTC with a negative BRAF V600E mutation in preoperative evaluation, the repeated BRAF V600E mutation testing found out 12 samples with BRAF V600E mutation. The true BRAF V600E mutation rate of Chinese PTC patients was 91.29%. Chinese patients with PTC have a higher frequency of BRAF V600E mutation. The BRAF V600E mutation testing affords a high diagnostic value in thyroid nodules with indeterminate cytology.

Somatic Mutation Profiling of Papillary Thyroid Carcinomas by Whole-exome Sequencing and Its Relationship with Clinical Characteristics

“…In our verification cohort, the mutation frequencies of BRAF, TP53, MSH3, and MSH6 were 45.31% (29/64), 34.38% (22/64), 7.81% (5/64), and 12.50% (8/64), respectively, which did not fully consistent with our WES results. This is probably the reason for the different samples and other factors, but it was within the range of mutation frequency reported in the previous studies 6 , 19 . We also found that in the 23 PTCs samples, BCR, CREB3L1, and MSH6 underwent frameshift changes, a type of variation likely to affect the structure and function of these 3 gene products in the PTCs.…”

“…Several important mutated genes, such as BRAF, TP53, MSH3, and MSH6, were selected to verify the mutation frequency, and found that the cohort verification results were not completely consistent with the results obtained by the WES. We believe that different samples, sampling conditions, operating procedures, and other factors may lead to the inconsistent results, but the mutation frequency is within the range reported previously 6 , 19 . Our verification cohort, at least to some extent, supported the authenticity of the somatic mutation profiling.…”

“…Previous studies demonstrated the presence of a universal mutation in the BRAF gene, regarded as a reliable molecular marker associated with oncogenesis, invasion, and prognosis in PTCs. It was reported that the prevalence of BRAF mutations in PTCs is 30-80% 25 , and Chinese patients with PTCs have a higher frequency of BRAF mutations 19 , 26 - 29 . In the present study, mutations in the BRAF gene were observed in 65% of the cases.…”

Herbal Active Ingredients: An Emerging Potential for the Prevention and Treatment of Papillary Thyroid Carcinoma

“…Both genetic and environmental factors act on thyroid cells and ultimately lead to the transformation of normal thyroid cells into tumor cells. During PTC pathogenesis, some critical genes (including BRAF, RET, KRAS, and PI3KCA) through mutation or chromosomal translocation continuously activate their dependent downstream signaling pathways, such as mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/AKT, nuclear factor-κB (NF-κB), and Notch-1, and thereby lead to cellular proliferation, migration, invasion, and angiogenesis [15][16][17]. Recently, emerging clinical trials and experimental researches also demonstrated that some noncoding RNA expressions, such as miRs-21, -34b, -221/222, lncRNA ATB, lncRNA H19, lncRNA HOXA-AS2, circITCH, and circZFR, showed significant association with aggressive clinicopathologic feature in PTC, including tumor size, lymphovascular invasion, lymph node metastases, and presence of BRAF V600E mutation [17][18][19][20][21].…”

SIRT1 Expression and BRAF V600E Mutation in Papillary Thyroid Cancer: Implications for Diagnosis and Prognosis

“…The BRAF V600E mutation, the T1799A transverse point mutation of BRAF that results in a valine-to-glutamic acid change in codon 600, which is the most common genetic alteration in PTC, was initially found in melanoma (8) and subsequently in other human cancers, including colorectal (9) and thyroid cancers (10). Studies have confirmed that the expression of the BRAF V600E mutant protein could constitutively activate the mitogen-activated protein kinase (MAPK) signaling pathway, which increases the recurrence and disease-specific mortality of PTC (11,12). This mutation constitutively activates the BRAF kinase and subsequently the MAPK signaling pathway (13,14).…”