TEST:

Afirma® Genomic Sequencing Classifier

Both molecular tests demonstrate high NPV but low specificity; neither is clearly superior. Future research should prioritise randomised controlled trials, long-term follow-up of unoperated nodules, and direct comparisons of molecular tests.

These guidelines emphasize the need for standardized protocols and equitable access to such testing. Molecular diagnostics should be embraced as complementary tools within multidisciplinary care to optimize patient outcomes while reducing unnecessary interventions in thyroid nodule management.

AUS-Nuclear carries a substantially higher ROM than AUS-Other, with a ROM (54.7%) comparable to the reported positive predictive values of molecular assays such as Afirma GSC (47%, 95% CI: 36%-58%) and ThyroSeq v3 (66%, 95% CI: 56%-75%). These findings support the clinical utility of the two-tiered AUS subclassification in enhancing risk stratification, particularly in settings where molecular testing is not routinely available.

Multiple signature expression profiles showed marked variation among American Thyroid Association risk classes and may help enhance preoperative prognostication. Although Invasion Score mirrors greater risk pathologic features, upregulated Sodium-Iodide Symporter Expression appears to protect from greater American Thyroid Association risk class, although further studies are needed to confirm.

FAT1 mutation has been previously associated with head and neck squamous cell carcinoma but has not been reported in the context of papillary thyroid cancer. FAT1 gene variation may be a novel mutation associated with papillary thyroid cancer.

In the validation cohort, made up of 75% women with a median age of 53 years, 51% of the samples were ruled out for high risk for invasion label with a 99% [95-100] NPV, and 53% were ruled out for high risk for LNM label with 100% [97-100] NPV. Gene expression-based classifiers that confidently, preoperatively rule out thyroid tumor invasion and lymph node metastasis may help personalize the surgical approach for individuals, reducing overtreatment, surgical complications, and postoperative hypothyroidism.

P=N/A, N=50, Recruiting, Columbia University | Trial completion date: Aug 2026 --> Aug 2027 | Trial primary completion date: Aug 2025 --> Aug 2026

Standardized protocols are needed to optimize clinical application. Further prospective studies should compare platforms and assess long-term outcomes and cost-effectiveness.

P=N/A, N=328, Active, not recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

GSC BCR and diagnostic performance of GSC testing may vary in AUS-N versus AUS-O subcategories. However, there were no statistically significant differences in GSC performance between single and repeat AUS cohorts.

The detection of BRAF fusions and their many partners was enabled by the Afirma XA exome-enriched RNASeq panel. Although BRAF fusions occurred in only 0.2% of thyroid nodules, they were GSC-Suspicious and lacked typical BRAF/RAS mutations. Interestingly, expression signatures associated with malignancy varied by fusion partner.

In older adolescents with ITN, the A firma GSC showed excellent performance when de fining a true negative result by histology or clinical follow-up. Our findings indicate that an A firma GSC-B result appears reassuring and may allow for a more conservative management strategy in younger patients with ITN.