Diagnostic Value of RAS Mutations in Indeterminate Thyroid Nodules

Area of Science:

• Endocrinology
• Oncology
• Molecular Diagnostics

Background:

• Fine-needle aspiration biopsy (FNAB) is crucial for thyroid nodule evaluation.
• Nondiagnostic or indeterminate cytology results from FNAB pose a clinical challenge.
• RAS (HRAS, KRAS, NRAS) mutations are investigated as potential biomarkers.

Purpose of the Study:

• To evaluate the diagnostic accuracy of HRAS, KRAS, and NRAS mutations in indeterminate thyroid nodules.
• To determine the sensitivity, specificity, and predictive values of RAS mutations for malignancy.

Main Methods:

• Systematic literature search of PubMed, Scopus, Embase, and CINAHL.
• Meta-analysis of 7 studies including 1025 patients with indeterminate thyroid nodules.
• Calculation of pooled sensitivity, specificity, positive/negative predictive values, and likelihood ratios.

Main Results:

• Pooled sensitivity for detecting cancer was 34.3% (95% CI, 19.8-50.6%).
• Pooled specificity was high at 93.5% (95% CI, 88.2-97.3%).
• Positive and negative predictive values were 78.0% and 64.0%, respectively, with 68.0% overall accuracy.

Conclusions:

• RAS mutation testing in indeterminate thyroid nodules has low sensitivity for cancer detection.
• The low sensitivity indicates that a negative RAS mutation test does not rule out malignancy.
• Current RAS mutation analysis is unlikely to alter clinical management decisions for these nodules.