Highly Sensitive and Specific Molecular Test for Mutations in the Diagnosis of Thyroid Nodules: A Prospective Study of BRAF-Prevalent Population

International Journal of Molecular Sciences

Yoo-Li Kim¹  HyunSook Yim¹  YoungLyun Oh²  JungHee Shin³  Jung-Han Kim⁴  JeeSoo Kim⁴  Jun-Ho Choe⁴  SoYoung Park⁵  YoonYoung Cho⁶  TaeHyuk Kim⁷  SunWook Kim⁷  JaeHoon Chung⁷  Chang-Seok Ki⁸ 

[1] BioSewoom Inc., Sungdong-gu, Seoul 04783, Korea;Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 06351, Korea;Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 06351, Korea;Division of Breast and Endocrine Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 06351, Korea;Division of Endocrinology and Metabolism, Department of Medicine, Korea University Ansan Hospital, Ansan 15355, Korea;Division of Endocrinology and Metabolism, Department of Medicine, Soonchunhyang University Bucheon Hospital, Bucheon 14584, Korea;Division of Endocrinology and Metabolism, Department of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 06351, Korea;Green Cross Genome, Yongin 16924, Korea;

关键词: molecular diagnostic technique;    fine-needle aspiration;    thyroid cancer;    BRAF-prevalent population;    prospective study;   

DOI  :  10.3390/ijms21165629

来源: DOAJ

【 摘 要 】

Molecular testing offers more objective information in the diagnosis and personalized decision making for thyroid nodules. In Korea, as the BRAF V600E mutation is detected in 70–80% of thyroid cancer specimens, its testing in fine-needle aspiration (FNA) cytology specimens alone has been used for the differential diagnosis of thyroid nodules until now. Thus, we aimed to develop a mutation panel to detect not only BRAF V600E, but also other common genetic alterations in thyroid cancer and to evaluate the diagnostic accuracy of the mutation panel for thyroid nodules in Korea. For this prospective study, FNA specimens of 430 nodules were obtained from patients who underwent thyroid surgery for thyroid nodules. A molecular test was devised using real-time PCR to detect common genetic alterations in thyroid cancer, including BRAF, N-, H-, and K-RAS mutations and rearrangements of RET/PTC and PAX8/PPARr. Positive results for the mutation panel were confirmed by sequencing. Among the 430 FNA specimens, genetic alterations were detected in 293 cases (68%). BRAF V600E (240 of 347 cases, 69%) was the most prevalent mutation in thyroid cancer. The RAS mutation was most prevalently detected for indeterminate cytology. Among the 293 mutation-positive cases, 287 (98%) were diagnosed as cancer. The combination of molecular testing and cytology improved sensitivity from 72% (cytology alone) to 89% (combination), with a specificity of 93%. We verified the excellent diagnostic performance of the mutation panel applicable for clinical practice in Korea. A plan has been devised to validate its performance using independent FNA specimens.

【 授权许可】

Unknown