miRNA expression can classify pediatric thyroid lesions and increases the diagnostic yield of mutation testing

Abstract

Background: Genetic alterations in multiple cell signaling pathways are involved in the molecular pathogenesis of thyroid cancer. Oncogene mutation testing and gene-expression profiling are routinely used for the preoperative risk management of adult thyroid nodules. In this study, we evaluated the potential value of miRNA biomarkers for the classification of pediatric thyroid lesions.Procedure: Double-blind case-control study with 113 resected pediatric lesions: 66 malignant and 47 benign. Quantitative and qualitative molecular data generated with a 10-miRNA expression panel (ThyraMIR) and a next-generation sequencing oncogene panel (ThyGeNEXT) were compared with clinicopathological parameters.Results: miRNAs were differentially expressed in benign versus malignant tumors with distinct expression patterns in different histopathology categories. The 10-miRNA classifier identified 39 (59%) malignant lesions with 100% specificity. A positive classifier score was associated with lymph node metastasis, extrathyroidal extension and intrathyroidal spread. Genetic alterations associated with increased risk for malignancy were detected in 35 (53%) malignant cases, 20 positive for point mutations in BRAF, HRAS, KRAS, NRAS, PIK3CA, or TERT and 15 positive for gene rearrangements involving ALK, NTRK3, PPARG, or RET. The 10-miRNA classifier correctly identified 11 mutation-negative malignant cases. The performance of the combined molecular test was 70% sensitivity and 96% specificity with an area under the curve of 0.924. Conclusions:These data suggest that the regulatory miRNA pathways underlying thyroid tumorigenesis are similar in adults and children. miRNA expression can identify malignant lesions with Abbreviations: CHOP, The Children's Hospital of Philadelphia; CI, confidence intervals; CLT, chronic lymphocytic thyroiditis; cPTC, classic papillary thyroid cancer; DH, diffuse hyperplasia; dsvPTC, diffuse sclerosing variant papillary thyroid cancer; DTC, differentiated thyroid cancer; FA, follicular adenoma; FNA, fine-needle aspiration; FTC, follicular thyroid cancer; fvPTC, follicular variant papillary thyroid cancer; mixPTC, mixed papillary thyroid cancer; MNG, multinodular goiter; NIFTP, noninvasive follicular thyroid neoplasm with papillary-like nuclear features; oPTC, oncocytic papillary thyroid cancer; OR, odds ratio; pFA, follicular adenoma with papillary changes.

Patterns and Predictors of Metastatic Spread to the Neck in Pediatric Thyroid Carcinoma

“…The most common mutations in our study were BRAF V600E and RET/PTC. This is similar to a study of 66 malignant cases in children whereby BRAF V600E, RET/PTC and RAS were the most common 22 . Results suggest that patients with a genetic mutation should be followed closely if neck dissection is not initially required.…”

“…Somatic genetic mutations were more common in patients requiring (68%) versus not requiring (38%) neck dissection. Although somatic genetic mutations have been correlated with more aggressive disease and lymph node involvement in adults, investigation into this relationship in children is just beginning 22 . The most common mutations in our study were BRAF V600E and RET/PTC.…”

Thyroseq v3, Afirma GSC, and microRNA Panels Versus Previous Molecular Tests in the Preoperative Diagnosis of Indeterminate Thyroid Nodules: A Systematic Review and Meta-Analysis

“…Based on the readings of the full-text articles, we excluded 28 articles for the following reasons: only enrolled nodules with benign test results (n = 4) ( 78 – 81 ) or suspicious test results (n = 1) ( 82 ), evaluated nodules with benign or malignant cytology (n = 2) ( 83 , 84 ), did not perform surgery and consequently did not provide reference standard in nodules with benign test results (n = 7) ( 85 – 91 ), an overlap of the participants with other studies (n = 8) ( 92 – 99 ), used freshly collected FNA samples as the reference standard (n = 1) ( 100 ), unavailable statistical analysis (n = 4) ( 13 , 22 , 101 , 102 ), and unavailable full-text article (n = 1). Finally, 40 articles met initial eligibility criteria and were systematically reviewed and abstracted.…”

Major Oncogenic Drivers and Their Clinicopathological Correlations in Sporadic Childhood Papillary Thyroid Carcinoma in Belarus

“…In the reports from other countries, a 9.0% (12/133) prevalence was found cumulatively in four studies of sporadic PTCs from the U.S. [29,[32][33][34]]. An 8.6% (3/35) prevalence was reported in a Brazilian study [35], and an 11.1% (1/9) in childhood PTC from Japan [36].…”