Discriminating Interpatient Variabilities of RAS Gene Variants for Precision Detection of Thyroid Cancer
Authors' conclusion
This diagnostic study delineated interpatient differences in RAS variants present in thyroid tumors with a variety of histopathological diagnoses. Discrimination of interpatient variabilities in RAS in combination with BRAF V600E and TERT promoter variants could facilitate cytology examinations in preoperative precision malignancy diagnosis among patients with thyroid nodules.
Study context
- Population
- Patients with thyroid nodules; surgically resected thyroid tumors (2016–2022) and residual thyroid fine-needle aspiration (FNA) biopsies (2020–2021), Mount Sinai Hospital, Toronto; 75.8% female, mean age 50.7 years438 tumors
- Participants
- 620 patients249 FNAs
- Comparison
- BRAF V600E + TERT promoter variant assays with vs without RAS variants
- Outcome
- Malignancy rates, sensitivity, specificity, PPV and NPV of RAS, BRAF V600E and TERT promoter variants vs surgical histopathologic diagnoses
Methodological detailsprospective, single-centre
- Prospective
- Single-centre
Performance
As reported in the abstract
Distinguishing malignant neoplasms from benign and NIFTP tumors
| Test or model | Sensitivity | Specificity |
|---|---|---|
| BRAF + TERT | 54.2% (95% CI, 48.8%-59.4%)Sensitivity on a scale from 0 to 100 percent | 100% (95% CI, 94.8%-100%)Specificity on a scale from 0 to 100 percent |
| RAS + BRAF + TERT | 70.5% (95% CI, 65.4%-75.2%)Sensitivity on a scale from 0 to 100 percent | 88.8% (95% CI, 79.8%-94.1%)Specificity on a scale from 0 to 100 percent |
Sensitivity
BRAF + TERT54.2% (95% CI, 48.8%-59.4%)
RAS + BRAF + TERT70.5% (95% CI, 65.4%-75.2%)
Sensitivity on a scale from 0 to 100 percentSpecificity
BRAF + TERT100% (95% CI, 94.8%-100%)
RAS + BRAF + TERT88.8% (95% CI, 79.8%-94.1%)
Specificity on a scale from 0 to 100 percentFurther findings
| Outcome | Values | P value |
|---|---|---|
| Mean (SD) VAF of RAS variants by histologyBetween Benign and NIFTP · no significant differences among benign, NIFTP and malignant | Benign mean 39.2% (SD 11.2%) · NIFTP mean 25.4% (SD 14.3%) · Malignant mean 33.4% (SD 13.8%) | P = 0.28 |
| Neoplasms at low risk of tumor recurrenceRAS variants vs RAS negative | RAS variants 60.7% · RAS negative 26.9% | P < 0.001 |
- Mean (SD) VAF of RAS variants by histology — RAS variant distribution: NIFTPs vs invasive encapsulated follicular variant PTC
- 41.7% vs 50.7%; P < .001
RAS variants in tumors
- Any RAS variant
- 89 (20.3%)
- NRAS
- 51 (11.6%)
- HRAS
- 29 (6.6%)
- KRAS
- 9 (2.1%)
- VAF range
- 0.15% to 51.53%
5 gene variants detected in FNAs
- Indeterminate FNAs
- 54 of 126 (42.9%)
- Nondiagnostic FNAs
- 18 of 76 (23.7%)
- All tumors with follow-up surgical pathology confirmed malignancy
- Median (IQR) follow-up 88 (50-156) days
Original publication
Discriminating Interpatient Variabilities of RAS Gene Variants for Precision Detection of Thyroid Cancer. JAMA Netw Open. Published 1 May 2024. doi:10.
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