Correlation of the Expression of BRAF V600E Mutation With Various Phenotypic Expressions of Thyroid Neoplasms

Aims We aimed to assess the incidence of the BRAF V600E mutation in thyroid neoplasms at a tertiary care center and its association with various phenotypic features. Methods and material We included all cases diagnosed as thyroid neoplasm in the past decade at the Department of Pathology of our institute and obtained their clinical details from the medical records department of the institute after obtaining permission from the authorities and due International Human Epigenome Consortium clearance. We included data on age, sex, clinical presentation, hormone status, and T and N status of the malignant neoplasms. Hematoxylin and eosin (H&E) slides of all cases were evaluated for the type of neoplasm, nuclear features, invasion into the capsule and vascular spaces, extrathyroidal extension, lymph node metastases, mitoses, necrosis, and presence/absence of amyloid. Paraffin blocks of sections with high tumor density and less normal tissue were chosen for evaluation after H&E staining. The slides showing tumors with large areas of hemorrhage, cystic change, or necrosis were excluded. Two primers were used to amplify a 339-bp fragment containing the V600E mutation in exon 15 of BRAF. Tissues were prepared from formalin-fixed paraffin-embedded (FFPE) blocks, and DNA was isolated using a standard protocol BRAF NF and BRAF NR Primer Standardized Protocol For FFPE Tissue DNA. Percentages and tables have been used for data presentation. Results Among 47 identified cases, 14 were positive for the BRAF V600E mutation and had papillary carcinoma (n = 9) or follicular neoplasms (n = 5; follicular adenoma, n = 3; follicular carcinoma, n = 2). In the BRAF-positive papillary carcinomas, five cases were aged 20-30 years, eight were female, eight (88.88%) were euthyroid, and one was hypothyroid. Furthermore, 55.55% (5/9 cases) of BRAF-positive cases were stage I, 33.3% (3/9 cases) were stage II, and 0.02% (1/9 cases) were stage III. Conclusions In our cohort, 31% of cases of papillary thyroid carcinoma (PTC) and 18.72% of follicular neoplasms expressed the BRAF V600E mutation. BRAF V600E mutation-positive papillary thyroid carcinomas consistently showed all characteristic nuclear features, such as nuclear crowding, overlapping, and grooves. Considering the greater prevalence in the younger age group, the importance of mutation surveillance in PTCs for a total thyroidectomy may be warranted in mutation-positive patients.

Automated summary

The study aimed to assess the incidence of the BRAF V600E mutation in thyroid neoplasms at a tertiary care center and its association with various phenotypic features. Results showed that in the cases, 31% of papillary thyroid carcinoma (PTC) and 18.72% of follicular neoplasms expressed the BRAF V600E mutation, displaying characteristic nuclear features.