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Analytic and clinical validity of thyroid nodule mutational profiling using droplet digital polymerase chain reaction
- Source :
- Journal of Otolaryngology-Head and Neck Surgery, Vol 47, Iss 1, Pp 1-9 (2018)
- Publication Year :
- 2018
- Publisher :
- BMC, 2018.
-
Abstract
- Background Recent guidelines for the management of thyroid nodules incorporate mutation testing as an adjunct for surgical decision-making, however current tests are costly with limited accuracy. Droplet digital PCR (ddPCR) is an ultrasensitive method of nucleic acid detection that is particularly useful for identifying gene mutations. This study aimed to assess the analytic and clinical validity of RAS and BRAF ddPCR mutational testing as a diagnostic tool for thyroid fine needle aspirate biopsy (FNAB). Methods Patients with thyroid nodules meeting indication for FNAB were prospectively enrolled from March 2015 to September 2017. In addition to clinical protocol, an additional FNAB was obtained for ddPCR. Optimized ddPCR probes were used to detect mutations including HRASG12 V, HRASQ61K, HRASQ61R, NRASQ61R, NRASQ61K and BRAFV600E. The diagnostic performance of BRAF and RAS mutations was assessed individually or in combination with Bethesda classification against final surgical pathology. Results A total of 208 patients underwent FNAB and mutational testing with the following Bethesda cytologic classification: 26.9% non-diagnostic, 55.2% benign, 5.3% FLUS/AUS, 2.9% FN/SPN, 2.4% SFM and 7.2% malignant. Adequate RNA was obtained from 91.3% (190) FNABs from which mutations were identified in 21.1% of HRAS, 11.5% of NRAS and 7.4% of BRAF. Malignant cytology or BRAFV600E was 100% specific for malignancy. Combining cytology with ddPCR BRAF600E mutations testing increased the sensitivity of Bethesda classification from 41.7 to 75%. Combined BRAFV600E and Bethesda results had a positive predictive value (PPV) of 100% and negative predictive value (NPV) of 89.7% for thyroid malignancy in our cohort. Conclusions DdPCR offers a novel and ultrasensitive method of detecting RAS and BRAF mutations from thyroid FNABs. BRAFV600E mutation testing by ddPCR may serve as a useful adjunct to increase sensitivity and specificity of thyroid FNAB.
- Subjects :
- Oncology
Thyroid nodules
Neuroblastoma RAS viral oncogene homolog
Male
medicine.medical_specialty
Biopsy, Fine-Needle
DNA Mutational Analysis
Thyroid Gland
lcsh:Surgery
030209 endocrinology & metabolism
Gene mutation
Malignancy
Polymerase Chain Reaction
Surgical pathology
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Humans
Digital polymerase chain reaction
HRAS
Thyroid Neoplasms
Thyroid Nodule
business.industry
Thyroid
Reproducibility of Results
DNA, Neoplasm
lcsh:RD1-811
Middle Aged
medicine.disease
medicine.anatomical_structure
Otorhinolaryngology
030220 oncology & carcinogenesis
Mutation
Surgery
Female
business
Subjects
Details
- Language :
- English
- ISSN :
- 19160216
- Volume :
- 47
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Otolaryngology - Head and Neck Surgery
- Accession number :
- edsair.doi.dedup.....8eefc66943a43f30be7a35d88513cba6
- Full Text :
- https://doi.org/10.1186/s40463-018-0299-2