126 chapter 2 RAS mutation in Bethesda III nodules Eight studies reported on RAS mutation analysis in a total of 1,320 Bethesda III nodules, 125 (9.5%) of which carried a RAS mutation. Histopathology was available for only 621 (47.2%) nodules with a conclusive index test: 63% (79/125) of the RAS mutation-positive Bethesda III nodules, 45.5% (542/1,190) of the RAS mutation-negative, and none of the five with nondiagnostic test results. Estimated pooled sensitivity, specificity, positive and negative LR are 19.1% (95% CI: 4.7%-53.2%), 96.4% (95% CI: 87.7%-99.0%), 5.37 (95% CI: 0.90-31.89) and 0.84 (95% CI: 0.62-1.13). The AUC is 0.84 (95% CI: 0.80-0.87) (Table 11, Figure 15, and Figure 16). RAS mutation in Bethesda IV nodules RAS mutation analysis in Bethesda IV nodules was reported in nine studies, including 1,105 nodules with an average malignancy rate of 26.5%. RAS mutation was reported in 12.7% (140/1,105) nodules, significantly more than 9.5% (125/1,320) in the Bethesda III group (Pearson χ2, p=0.01). Histopathology was available for 1,005 (94.5%) Bethesda IV nodules with a conclusive RAS mutation analysis, including 138 (99.6%) of the RAS mutation- positive nodules. I2 is 72.7% for sensitivity and 41.8% for specificity. Estimated pooled sensitivity, specificity, positive and negative LR are 33.3% (95% CI: 21.1%-48.3%), 96.6% (95% CI: 94.3%-98.0%), 9.69 (95% CI: 4.94-19.00) and 0.69 (95% CI: 0.56-0.85). The AUC is 0.94 (95% CI: 0.92-0.96) (Table 12, Figure 17 and Figure 18). Figure 16. SROC curve of RAS mutation analysis – Bethesda III Summary receiver operating characteristic plot showing sensitivity versus 1-specificity of RAS mutation analysis in Bethesda III thyroid nodules with available histopathology. AUC = 0.84 (95% CI: 0.80-0.87). AUC, area under the curve; HSROC, hierarchical summary receiver operating characteristic.
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