Bangaraiahgari Ramesh, Panchangam Ramakanth Bhargav, Puthenveetil Pradeep, Mayilvaganan Sabaretnam, Bangaraiahgari Rajesh, Banala Rajkiran Reddy, Karunakaran Poongkodi, Md Rafi
Department of Biochemistry, Surabhi Medical College, Hyderabad, Telangana, India.
Endocare Hospital, Suryaraopeta, Vijayawada, AP, 520002, India.
Ann Med Surg (Lond). 2020 Dec 2;60:695-700. doi: 10.1016/j.amsu.2020.11.069. eCollection 2020 Dec.
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 and clinical significance of these somatic mutations in surgical tissue samples.
This retrospective 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 100 benign thyroid adenomas (BTA) and 100 papillary thyroid carcinoma (PTC) cases. Archived tumour tissue samples of selected cases were retrieved. 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.
Homozygous mutations in -RAS were found in 36/100 (36%) of BTA and 7/100 (7%) of PTC cases. No H-RAS or K-RAS mutations were found in both groups. Homozygous mutations were found in BRAF gene in 4/100 (4%) of BTA cases and 52/100 (52%) of PTC cases. The differences were statistically significant.
Similar -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.
甲状腺结节中的腺瘤-癌序列是一种神秘的现象。基因组学是解决这一假说的唯一确定性方法。腺瘤和乳头状癌往往分别在RAS和高度特异性的BRAF基因中发生突变。在此背景下，我们着手研究手术组织样本中这些体细胞突变的发生率及其临床意义。
本回顾性研究针对接受手术治疗的甲状腺结节患者开展。获得了机构伦理委员会的批准。诊断基于生化确认、影像学检查、细针穿刺细胞学检查，随后经组织病理学确诊。我们选取了100例良性甲状腺腺瘤（BTA）和100例乳头状甲状腺癌（PTC）病例。检索所选病例的存档肿瘤组织样本。在对样本进行适当处理后，进行DNA提取、cDNA制备、PCR扩增，并作为RAS（H-、K-、N-）和BRAF基因的突变分析的一部分，应用4组引物。
在100例BTA病例中有36/100（36%）发现-RAS纯合突变，在100例PTC病例中有7/100（7%）发现。两组均未发现H-RAS或K-RAS突变。在100例BTA病例中有4/100（4%）发现BRAF基因纯合突变，在100例PTC病例中有52/100（52%）发现。差异具有统计学意义。
相似的-RAS和BRAF突变在良性和恶性甲状腺结节中均很普遍，为它们之间的联系提供了一些证据。尽管证据并不充分，但我们认为甲状腺结节中存在腺瘤-癌序列的可能性。
