RAS mutations in indeterminate thyroid nodules are predictive of the follicular variant of papillary thyroid carcinoma

• Published in: Clinical endocrinology (Oxford) 2015-05, Vol.82 (5), p.760-766
• Main Authors: An, Jee Hyun, Song, Kee-Ho, Kim, Suk Kyeong, Park, Kyoung Sik, Yoo, Young Bum, Yang, Jung-Hyun, Hwang, Tae Sook, Kim, Dong-Lim
• Format: Article
• Language: English
• Subjects: Adenocarcinoma, Follicular - diagnostic imaging; Adenocarcinoma, Follicular - genetics; Adult; Aged; Biopsy, Fine-Needle; Carcinoma - diagnostic imaging; Carcinoma - genetics; Carcinoma, Papillary; DNA Mutational Analysis; Female; Genes, ras; Humans; Male; Middle Aged; Mutation; Point Mutation; Predictive Value of Tests; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins p21(ras) - genetics; ras Proteins - genetics; Reproducibility of Results; Sensitivity and Specificity; Thyroid Cancer, Papillary; Thyroid Neoplasms - diagnostic imaging; Thyroid Neoplasms - genetics; Thyroid Nodule - diagnostic imaging; Thyroid Nodule - genetics; Thyroid Nodule - pathology; Ultrasonography
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1111/cen.12579

Summary Objective RAS mutations are the most common mutations in thyroid nodules with indeterminate cytology by fine‐needle aspiration cytology (FNAC), and are mutually exclusive with BRAF mutations. However, the diagnostic utility of RAS mutation analysis is uncertain. We evaluated the diagnostic utility of RAS mutation analysis in indeterminate thyroid nodules. Design, patients, and measurements A total of 155 thyroid nodules (90 benign and 65 indeterminate) negative for BRAFV600E mutations on FNAC were analysed for mutations in RAS codon 61 using pyrosequencing methods. We evaluated diagnostic accuracy of RAS mutation for predicting thyroid malignancy based on the surgical pathologic diagnosis. Results Among the 65 BRAFV600E‐negative indeterminate thyroid nodules identified by FNAC, 25 (38·5%) exhibited point mutations in RAS 61 consisting of 18 NRAS 61 (72%), and 7 HRAS 61 (28%) mutations. In contrast, only five of 90 (5·6%) nodules with benign cytology had RAS mutations. Only two of 25 (8·0%) RAS 61+ indeterminate nodules exhibited malignant ultrasonographic features. Of the 15 patients with RAS 61+‐indeterminate nodules who underwent thyroid surgery, 14 (93·3%) were diagnosed as malignant, including 13 follicular variant of papillary thyroid carcinomas (FVPTC), and one follicular thyroid carcinoma (FTC). The average tumour size was 1·79 ± 0·62 cm. Multifocality was seen in 28·6% of cases, with 7·1% exhibiting extrathyroidal extension; no lymph node or distant metastases were evident. Based on the surgical pathologic diagnosis results, preoperative RAS 61 mutation analysis on FNAC exhibited 93·3% sensitivity, 75·0% specificity, 93·3% positive predictive value, 75·0% negative predictive value and 89·5% diagnostic accuracy for predicting malignancies. Conclusion Our results suggest that RAS mutation analysis holds great promise as a preoperative diagnostic tool for predicting FVPTC in cytologically and sonographically indeterminate nodules negative for BRAF mutations.