Next Generation Sequence-Based Targeted Somatic Mutation Analysis in Thyroid Nodules with Pathologically Diagnosed as Indeterminate Cytology

Project no. 22916 · Status: Kapanmış · 2021

Summary

Objective: Thyroid nodules represent a common problem in the population. The most crucial step following the detection of a thyroid nodule is to estimate the malignancy risk. For this, it is essential to collect clues about the nodule by investigating the risk factors of the patient, performing a physical examination, and ultrasonography. FNAB allows the examine the nodule's cytopathological characters. The approach to the nodules with indeterminate cytology is still challenging in daily practice. Molecular profiling has recently become one of the promising options. In our study; somatic mutation analysis was performed on nodules with indeterminate cytology. It aims to help identify nodule characters as malign or benign and search for markers to will help clinical management.Materials and Methods: Aspiration samples from 20 thyroid nodules with indeterminate cytology were included in our study. The specimens belonged to patients who had undergone surgery, and because of that, surgical pathology results were available. A next-generation sequencing panel containing 67 genes was used to molecularly profile the samples. The results were compared with the pathology of surgery material data, which is accepted as the gold standard. Sensitivity, specificity, PPV, and NPV were calculated.Results: The study detected variants of 6 different genes (BRAF, NRAS, PTEN, TERT, PIK3CA, TP53) in 10 of 20 samples. Surgical pathology results of 15 samples were malignant and 5 samples were benign. The malignant pathology consisted of 10 PTCs and 5 PMCs. One patient had lymph node metastasis (Stage IVA), one patient had a tumor of 4.2 cm (Stage III), and one had a tumor of 2.2 cm (Stage II). There were nine malignant and one benign surgical pathology in the patient group with variants. The mean age of the samples with variants was 56, and 46 in the non-variant group. The test was calculated as NPV: 40%, PPV: 90%, specificity: 60%, sensitivity: 80%.Conclusion: All samples were able to obtain a sufficient amount of DNA for the study. According to the detected molecular markers, at least 9 patients could have been managed correctly without the need for a repeat FNAB. This study underlines the practical clinical utility of molecular tests in the management of nodules with indeterminate cytology. Hence it is the first study about the molecular markers in thyroid nodules in our country, it is aimed to lead the following studies.Key Words: FNAB; Thyroid nodules; Thyroid cancer, NGS

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