Facilitation of Definitive Cancer Diagnosis With Quantitative Molecular Assays of BRAF V600E and TERT Promoter Variants in Patients With Thyroid Nodules
Authors' conclusion
This diagnostic study suggests that sensitive quantitative VAF assays of BRAF V600E and TERT promoter variants can elucidate the interpatient variability in tumors and facilitate a definitive cancer diagnosis of thyroid nodules by differentiating the variation extent of genomic variants, even at low VAFs.
Study context
- Population
- Surgically resected thyroid tumors ≥1 cm (2016–2020) and residual thyroid nodule fine-needle aspiration (FNA) biopsy specimens (2020–2021), Mount Sinai Hospital, Toronto; 580 patients, 75.2% femalespecimens from 580 patients
- Participants
- 595 participants
- Comparison
- Quantitative variant allele fraction (VAF) assays of BRAF V600E and TERT promoter variants vs histopathologic diagnosis
- Outcome
- Association of BRAF V600E and TERT promoter VAFs with histologic diagnosis and histopathologic features; diagnostic utility (ROC, sensitivity, specificity, PPV, NPV) vs follow-up histopathology
Methodological detailssingle-centre
- Single-centre
Performance
As reported in the abstract
- Malignancy stratified in indeterminate FNA cases
- 40 of 183 (21.9%)
- Sensitivity
- 93.8% (95% CI, 67.7%-99.7%)
- Specificity
- 90.0% (95% CI, 75.4%-96.7%)
- PPV
- 78.9% (95% CI, 53.9%-93.0%)
- NPV
- 97.3% (95% CI, 84.2%-99.9%)
- Agreement of FNA vs surgical tissue VAF assays
- κ = 0.793, P < .001
Further findings
Variant prevalence in 378 resected tumors
- BRAF V600E present
- 162 tumors (42.9%)
- BRAF V600E low VAF ≤1%
- 26 (16.0%)
- BRAF V600E high VAF >1%
- 136 (84.0%)
- TERT promoter variants present
- 49 tumors (13.0%)
- C228T variants
- 45 (91.8%); 15 (33.3%) low VAF ≤1%, 30 (66.7%) high VAF >1%
- C250T variants
- 4 (8.2%), VAFs between 40.0% and 47.0%
High VAFs and aggressive histopathologic features
- Significant association between high VAFs of either variant individually or different VAF levels of both in coexistence and aggressive histopathologic features
Intermediate-to-high risk of recurrence, excluding low VAFs
- OR
- 5.3 (95% CI, 1.9-14.6; P = .001)
Agreement of FNA vs surgical tissue VAF assays
- κ
- 0.793 (P < .001)
Original publication
Facilitation of Definitive Cancer Diagnosis With Quantitative Molecular Assays of BRAF V600E and TERT Promoter Variants in Patients With Thyroid Nodules. JAMA Netw Open. Published 3 July 2023. doi:10.
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