Expression of B-type RAF V600E in Thyroid Carcinoma and its Association with Histological Type

Abstract

Introduction: Thyroid cancer is one of the most common cancers amongst all endocrine cancers. Incidence of thyroid malignancy is about 3-4% of all malignancy in India and 80% of thyroid malignancy belongs to Papillary Thyroid Carcinoma (PTC). Factors affecting the prognosis of PTC include patient’s gender, age, histological findings, tumour size, lymph node metastasis, extrathyroidal extension, and remote metastasis. Presence of B-type RAF V600E (BRAF V600E) mutation in thyroid carcinoma patients tends to present with more aggressive clinicopathological behaviours of PTC, prompting more aggressive radioiodine treatment. Aim: To find out the frequency of occurrence and expression of BRAF V600E mutation by Immunohistochemistry (IHC) in thyroid cancer and its association with histological type and Tumour Nodes Metastases (TNM) Staging. Materials and Methods: The present observational retrospective study included patients treated for thyroid carcinoma between January 2014 to February 2019 at RL Jalappa hospital and Research centre, Kolar, Karnataka, India. The IHC was done with rabbit monoclonal anti-BRAF V600E antibody IgG Clone RM8 (VE1). Clinical records, Fine Needle Aspiration Cytology (FNAC) diagnosis were analysed for 45 thyroid carcinoma cases. Immunopositivity was scored positive when unambiguous clear cytoplasmic staining for the antibody was observed in tumour cells. Categorical data was presented in the form of frequencies and proportions and continuous data was presented as mean and standard deviation. The t-test were applied to find out the difference in means among the groups. The p-value <0.05 was considered statistically significant. Results: Out of total 45 cases, 18 were classical PTC, 18 were Follicular Variant of Papillary Thyroid Cancer (FV-PTC), 4 were micropapillary carcinomas, 3 were Follicular carcinomas, 1 was Oncocytic variant of PTC and 1 undifferentiated thyroid carcinoma. Out of total 45 cases, 33 cases (73%) were found to be BRAF V600E positive and 12 (26%) were negative for BRAF V600E. Out of the total 33 BRAF V600E positive cases, 19 cases showed strong staining, 14 cases showed moderately positive staining. Conclusion: The PTC is the most frequent type of thyroid carcinoma amongst all the sub-types. BRAF V600E expression is commonly seen in higher tumour size (T3, T4) and classical PTC. Tumours with extrathyroidal extension and capsular invasion showed strong positivity.