Department of Endocrinology and Metabolism, Institute of Post-Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, India.
J Clin Endocrinol Metab. 2021 Apr 23;106(5):e2262-e2270. doi: 10.1210/clinem/dgab030.
Molecular testing is increasingly used to identify malignancy in thyroid nodules (especially indeterminate category). Measurement of cell-free DNA (cfDNA) levels from plasma has been useful in diagnosis of cancers of other organs/tissues; herein we analyze cfDNA levels in patients with thyroid nodules to explore the possibility of establishing a cutoff for identification of malignancy.
Patients underwent ultrasonography (USG) and USG-guided fine needle aspiration as well as surgery, where indicated. Cell-free DNA was extracted from plasma and quantified. In initial analysis (determination of cutoff), cfDNA levels were compared between Bethesda 2 and Bethesda 5 &6 to establish a cutoff value that could differentiate malignant from benign nodules. In the subsequent analysis, the aforementioned cutoff was applied (validation of cutoff) to those with indeterminate nodules to check ability to predict malignancy.
Fine needle aspiration (n = 119) yielded patients with Bethesda 2 (n = 69) Bethesda 5 & 6 (n = 13) who underwent histopathological confirmation. Cell-free DNA levels in these 2 groups were 22.85 ± 1.27 and 96.20 ± 8.31 (ng/mL) respectively. A cfDNA cutoff of 67.9 ng/mL, with area under the curve of 0.992 (95% CI, 0.97-1.0) with 100% sensitivity and 93% specificity was established to identify malignant lesions. Indeterminate group (Bethesda 3 & 4) underwent surgery (malignant n = 24), (benign n = 13), and using the previously identified cutoff for cfDNA, we were able to identify malignant lesions with a sensitivity of 100% and specificity of 92.3%. There was a very strong agreement between cfDNA-based classification with histopathology-based classification of benign and malignant nodules (Cohen's kappa 0.94; P < 0.001).
Plasma cfDNA estimation could help differentiate malignant from benign thyroid nodules.
分子检测越来越多地用于确定甲状腺结节（尤其是不确定类别）的恶性程度。从血浆中测量游离细胞 DNA (cfDNA) 水平已被证明有助于诊断其他器官/组织的癌症；在此，我们分析甲状腺结节患者的 cfDNA 水平，以探讨建立鉴别良恶性的截止值的可能性。
患者接受超声检查 (USG) 和 USG 引导下的细针抽吸活检，以及必要时的手术。从血浆中提取游离细胞 DNA 并进行定量。在初步分析（确定截止值）中，比较 Bethesda 2 与 Bethesda 5 和 6 之间的 cfDNA 水平，以建立一个可以区分良恶性结节的截止值。在随后的分析中，应用上述截止值（验证截止值）对不确定结节患者进行分析，以检查其预测恶性肿瘤的能力。
细针抽吸活检（n=119）获得了 Bethesda 2（n=69）和 Bethesda 5 和 6（n=13）的患者，这些患者均经过组织病理学证实。这两组的 cfDNA 水平分别为 22.85±1.27 和 96.20±8.31（ng/ml）。确定了 67.9ng/ml 的 cfDNA 截止值，其曲线下面积为 0.992（95%CI，0.97-1.0），具有 100%的敏感性和 93%的特异性，可用于识别恶性病变。不确定组（Bethesda 3 和 4）接受了手术（恶性 n=24）、（良性 n=13），并使用之前确定的 cfDNA 截止值，我们能够以 100%的敏感性和 92.3%的特异性识别恶性病变。cfDNA 分类与组织病理学分类之间具有很强的一致性（良性和恶性结节的 Cohen's kappa 0.94；P<0.001）。
血浆 cfDNA 估计有助于区分甲状腺良恶性结节。
