Endocrine Abstracts

Introduction: The adenoma- carcinoma sequence in thyroid nodules is an enigmatic phenomenon. Genomics is the only definitive modality to resolve this hypothesis. Adenomas and papillary carcinomas tend to have mutations in RAS and highly specific BRAF gene respectively. In this context, we set out study the prevalence of these somatic mutations in surgical tissue samples.

Material and Methods: This prospective study was conducted on surgically managed thyroid nodule patients. Institutional ethical committee approval was obtained. Diagnosis was based on biochemical confirmation, imaging, fine needle aspiration cytology and later confirmed by histopathology. We selected 28 benign thyroid adenomas (BTA) and 24 papillary thyroid carcinoma (PTC) cases. Tumour tissue samples were taken from ex-vivo thyroidectomy specimen within operation theatre. After appropriate processing of samples, DNA extraction, cDNA preparation, PCR amplification, application of 4 sets of Primers were performed as part of mutational analysis of RAS (H-,K-,N-) and BRAF genes.

Results: Homozygous mutations in N-RAS were found in 10/28 (36%) of BTA and 1/25 (4%) of PTC cases. No H-RAS or K-RAS mutations were found in both groups. Homozygous mutations were found in BRAF gene in 3/28 (11%) of BTA cases and 11/24 (46%) of PTC cases. The differences were statistically significant.

Conclusions: N-RAS and BRAF mutations were prevalent in both benign and malignant thyroid nodules giving some evidence for linkage between them. Though not robust, we opine that there is possibility of adenoma- carcinoma sequence in thyroid nodules. BRAF and RAS mutations appear to be specific to PTC and BTA respectively. We need larger multi-institutional studies to justify this observation in future.