Molecular Diagnosis Using Residual Liquid-Based Cytology Materials for Patients with Nondiagnostic or Indeterminate Thyroid Nodules.
BACKGROUND
Molecular analysis for common somatic mutations in thyroid cancer can improve diagnostic accuracy of fine-needle aspiration cytology (FNAC) in the nondiagnostic or indeterminate category of thyroid nodules. In this study, we evaluated the feasibility of molecular diagnosis from residual liquid-based cytology (LBC) material after cytological diagnosis.


METHODS
This prospective study enrolled 53 patients with thyroid nodules diagnosed as nondiagnostic, atypia of undetermined significance (AUS), or follicular lesion of undetermined significance (FLUS) after FNAC. DNAs and RNAs were isolated from residual LBC materials. BRAF(V600E) and RAS point mutations, PAX8/peroxisome proliferator-activated receptor γ (PPARγ), RET/PTC1, and RET/PTC3 rearrangements were evaluated by real-time polymerase chain reaction and pyrosequencing.


RESULTS
All DNAs from 53 residual LBC samples could be analysed and point mutations were detected in 10 samples (19%). In 17 AUS nodules, seven samples (41%) had point mutations including BRAF (n=4), NRAS (n=2), and KRAS (n=1). In 20 FLUS nodules, three samples (15%) had NRAS point mutations. RNA from only one FLUS nodule could be analysed for rearrangements and there was no abnormality.


CONCLUSIONS
Molecular analysis for BRAF and RAS mutations was feasible in residual LBC materials and might be useful for diagnosis of indeterminate thyroid nodules.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Hyemi
http://orcid.org/0000-0003-4257-3133
H
Kwon
Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Won Gu
http://orcid.org/0000-0002-8404-7759
WG
Kim
Division of Endocrinology and Metabolism, Department of Oncology and Arnie Charbonneau Cancer Institute, Cummings School of Medicine, University of Calgary, Calgary, AB, Canada.
Markus
M
Eszlinger
Division of Endocrinology and Metabolism, Department of Oncology and Arnie Charbonneau Cancer Institute, Cummings School of Medicine, University of Calgary, Calgary, AB, Canada.
Ralf
R
Paschke
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Dong Eun
http://orcid.org/0000-0002-9583-9794
DE
Song
Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Mijin
http://orcid.org/0000-0002-1538-8859
M
Kim
Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Suyeon
http://orcid.org/0000-0002-0607-281X
S
Park
Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Min Ji
http://orcid.org/0000-0002-1297-107X
MJ
Jeon
Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Tae Yong
http://orcid.org/0000-0003-4982-4441
TY
Kim
Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Young Kee
http://orcid.org/0000-0002-7911-9471
YK
Shong
Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. kimwb@amc.seoul.kr.
Won Bae
http://orcid.org/0000-0003-4544-1750
WB
Kim
Biopsy, fine-needle; Molecular diagnostic techniques; Thyroid aspiration; Thyroid neoplasms; Thyroid nodule