Dutta Susmita, Tarafdar Soham, Mukhopadhyay Pradip, Bhattacharyya Nitai P, Ghosh Sujoy
Department of Endocrinology, Institute of Post Graduate Medical Education & Research, Kolkata, India.
Eur J Endocrinol. 2023 Jan 10;188(1). doi: 10.1093/ejendo/lvac018.
This proof-of-concept paper demonstrates that driver mutations can be detected in plasma in differentiated thyroid tumors, and we were able to detect mutations in upto 80% malignant thyroid nodules. Additionally, cancer subtypes could also be predicted using a 8-gene panel. In almost 90% follicular adenoma, rat sarcoma virus (RAS) mutations were detectable. There was a strong agreement between driver mutations found in plasma samples, FNAC materials, and histopathology samples. This has potential as a noninvasive, preoperative diagnostic tool (particularly of clinical importance in indeterminate nodules) and may help in detection of residual tumor after surgery. Future research is warranted to test the role of this tool to detect tumor recurrence.
Ultrasonographic (USG) evaluation and fine-needle aspiration (FNA) are cornerstone for evaluation of thyroid neoplasm. Molecular technique including detection of driver mutation from FNA cytology (FNAC) material is an established modality. In this study, we explored the feasibility of using plasma cell-free nucleic acids to identify known driver mutations in differentiated thyroid neoplasm.
Patients presenting with thyroid nodules underwent USG with Thyroid Image Reporting and Data Systems scoring and FNAC (Bethesda classification). All patients in Bethesda 3, 4, 5, 6 underwent surgery and histopathological confirmation. Patients in Bethesda 2 (cosmetic concerns, compressive symptoms) underwent surgery, and rest were presumed benign on the basis of USG, FNAC features, and clinical followup.).
Endocrinology clinic.
Subjects with thyroid nodule.
INTERVENTION(S) OR EXPOSURE(S): None.
MAIN OUTCOME(S) AND MEASURE(S): Plasma sample, FNA, and histopathology material were evaluated for driver mutations (8-gene panel comprising BRAF-V600E, RET/PTC3, RET/PTC1, TERT promoter, HRAS, NRAS, KRAS, and PAX8-PPARG).
A total of 223 subjects were recruited; of these 154 were benign and 69 had differentiated thyroid cancer. We were able to detect driver mutation from plasma in 55 subjects (79.71%) of all malignant patients, and 11 patients in benign category had RAS mutation (follicular adenoma). Rest of the benign nodules did not have any detectable driver mutations.
Plasma might be a viable noninvasive alternative source for detection of driver mutations (8-gene panel) in subjects with differentiated thyroid tumors and may have significant clinical utility.
这篇概念验证论文表明，在分化型甲状腺肿瘤的血浆中可检测到驱动突变，并且我们能够在高达80%的恶性甲状腺结节中检测到突变。此外，还可使用一个8基因组合预测癌症亚型。在近90%的滤泡性腺瘤中可检测到大鼠肉瘤病毒（RAS）突变。血浆样本、细针穿刺活检（FNAC）材料和组织病理学样本中发现的驱动突变之间存在高度一致性。这具有作为一种非侵入性术前诊断工具的潜力（尤其是在不确定结节中具有重要临床意义），并可能有助于术后检测残留肿瘤。未来有必要进行研究以测试该工具在检测肿瘤复发中的作用。
超声（USG）评估和细针穿刺抽吸（FNA）是评估甲状腺肿瘤的基石。包括从FNA细胞学（FNAC）材料中检测驱动突变在内的分子技术是一种既定的方法。在本研究中，我们探讨了使用血浆游离核酸来识别分化型甲状腺肿瘤中已知驱动突变的可行性。
患有甲状腺结节的患者接受了USG检查，并进行了甲状腺影像报告和数据系统评分以及FNAC（贝塞斯达分类）。所有贝塞斯达分类为3、4、5、6级的患者均接受了手术及组织病理学确诊。贝塞斯达分类为2级（美容需求、压迫症状）的患者接受了手术，其余患者根据USG、FNAC特征和临床随访被推测为良性。
内分泌科门诊。
患有甲状腺结节的受试者。
无。
对血浆样本、FNA和组织病理学材料进行驱动突变评估（由BRAF-V600E、RET/PTC3、RET/PTC1、端粒酶逆转录酶（TERT）启动子、HRAS、NRAS、KRAS和PAX8-PPARG组成的8基因组合）。
共招募了223名受试者；其中154例为良性，69例患有分化型甲状腺癌。我们能够在所有恶性患者中的55名受试者（79.71%）的血浆中检测到驱动突变，11例良性受试者有RAS突变（滤泡性腺瘤）。其余良性结节未检测到任何驱动突变。
血浆可能是检测分化型甲状腺肿瘤患者驱动突变（8基因组合）的一种可行的非侵入性替代来源，可能具有显著的临床应用价值。
