The Significance of RAS -Like Mutations and MicroRNA Profiling in Predicting Malignancy in Thyroid Biopsy Specimens
ENDOCRINE PATHOLOGY(2022)
摘要
In cytologically indeterminate thyroid nodules undergoing molecular testing, estimated risk of malignancy is variable. Identification of a non-cancer-specific mutation ( RAS -like) confirms a neoplastic process but does not differentiate between benign, malignant, and low-risk neoplasms. This study aims to retrospectively evaluate institutional experience of Interpace (ThyGeNEXT ® and ThyraMIR ® ; Pittsburgh, PA) testing and to determine the rate of malignancy in resected nodules, stratified by mutational analysis and microRNA profile. Of 1917 fine need aspirations, 140 (7.3%) underwent Interpace testing: 47 (33.6%) were molecular-not-benign (harbored mutation, fusion, and/or positive miRNA) and 93 (66.4%) were molecular-benign (no mutations or fusions and negative microRNA). Surgery was spared in 79.6% of molecular-benign and 61.4% of all tested patients. Fifty-four (38.6%) underwent resection. Seventeen (89.5%) of the resected molecular-benign were benign and 2 were malignant. Thirteen (37.1%) of the resected molecular-not-benign were benign, 7 (20%) were noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), and 15 (42.9%) were malignant ( p < 0.05, negative predictive value (NPV) 89.4–95.6%, positive predictive value (PPV) 22.3–42.8%). Most molecular-not-benign (72.3%) had RAS -like mutation. Twenty-three were resected: 3 were malignant and 7 were NIFTP. Nodules with non- RAS -like mutations ( BRAF V600E-like, others) were more likely to be malignant than RAS -like ( H/N/KRAS , BRAF K601E) ( p < 0.05, NPV 86.9–96.5%, PPV 100%). Most nodules had RAS -like mutations and most were benign or low-risk neoplasms (NIFTP). This study supports the role of histologic examination in the distinction of malignancy in RAS -like thyroid neoplasms and underscores the role of molecular testing in risk stratification, patient counseling, and operative management.
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关键词
Thyroid biopsy,Molecular testing,Fine needle aspiration,MicroRNA profile,RAS-like mutation
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