Perumal Prasanna V, Siddaraju Neelaiah, Saxena Sunil K, Rajendiran Soundravally, Bhat Ramachandra V
Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, IND.
ENT, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, IND.
Cureus. 2023 Sep 29;15(9):e46206. doi: 10.7759/cureus.46206. eCollection 2023 Sep.
Background Follicular-patterned lesions are a major gray zone in thyroid cytopathology. The recently introduced 2022 World Health Organization (WHO) classification emphasizes the importance of genetic alterations in thyroid neoplasms with the introduction of certain newer terminologies that are expected to cause remarkable changes in cytopathologic and histopathologic reporting. Although molecular assays such as the Afirma gene expression classifier and the ThyroSeq are already in use, there has been an ongoing search for further reliable molecular markers. The growth differentiation factor-15 (GDF-15) is one among them. This study aimed to determine the diagnostic utility of GDF-15 mRNA expression in frozen tissue and fine-needle aspiration (FNA) samples from follicular-patterned thyroid lesions and neoplasms. Methodology The real-time quantitative polymerase chain reaction was performed on 75 frozen tissue and FNA samples each from 19 cases of follicular thyroid hyperplasia (FTH), 10 nodular goiters (NGs), 17 follicular thyroid adenomas (FTAs), eight follicular thyroid carcinomas (FTCs), 12 follicular variant of papillary thyroid carcinomas (FVPTCs), and nine classic papillary thyroid carcinomas (CPTCs) that were diagnosed according to the 2017 WHO classification of thyroid neoplasms. The GDF-15 mRNA expression in all these cases was assessed and compared with the control thyroid tissue samples. One-way analysis of variance and the Kruskal-Wallis test were performed using GraphPad Prism 8 software to determine the significance of differences in the GDF-15 mRNA levels among various thyroid lesions. Results A higher GDF-15 mRNA expression was noted in the malignant thyroid neoplasms including FTC, FVPTC, and CPTC in comparison to FTA, with a fold change between the malignant and benign groups being more than 244.18 times. A difference in the fold change was noted between FTH and FTA with an increase in GDF-15 mRNA level in the latter, which was statistically not significant. Conclusions The fact that GDF-15 mRNA was studied both on fine-needle aspiration cytologic and the frozen tissue material and that the majority of the lesions studied were follicular-patterned establishes the GDF-15 as a potential marker not only for diagnosing malignant thyroid neoplasms of the follicular epithelium but also in distinguishing benign and malignant follicular-patterned neoplasms of the thyroid.
滤泡样病变是甲状腺细胞病理学中的一个主要灰色地带。最近推出的2022年世界卫生组织（WHO）分类通过引入一些新术语强调了甲状腺肿瘤基因改变的重要性，这些新术语预计会给细胞病理学和组织病理学报告带来显著变化。尽管诸如Afirma基因表达分类器和ThyroSeq等分子检测方法已经在使用，但人们一直在寻找更可靠的分子标志物。生长分化因子15（GDF-15）就是其中之一。本研究旨在确定GDF-15 mRNA表达在滤泡样甲状腺病变和肿瘤的冰冻组织及细针穿刺（FNA）样本中的诊断效用。
对根据2017年WHO甲状腺肿瘤分类诊断的19例滤泡性甲状腺增生（FTH）、10例结节性甲状腺肿（NG）、17例滤泡性甲状腺腺瘤（FTA）、8例滤泡性甲状腺癌（FTC）、12例甲状腺乳头状癌滤泡变体（FVPTC）和9例经典甲状腺乳头状癌（CPTC）的75份冰冻组织和FNA样本进行实时定量聚合酶链反应。评估所有这些病例中GDF-15 mRNA的表达，并与对照甲状腺组织样本进行比较。使用GraphPad Prism 8软件进行单因素方差分析和Kruskal-Wallis检验，以确定各种甲状腺病变中GDF-15 mRNA水平差异的显著性。
与FTA相比，包括FTC、FVPTC和CPTC在内的恶性甲状腺肿瘤中GDF-15 mRNA表达更高，恶性组与良性组之间的倍数变化超过244.18倍。FTH和FTA之间的倍数变化存在差异，后者的GDF-15 mRNA水平升高，但在统计学上不显著。
GDF-15 mRNA在细针穿刺细胞学和冰冻组织材料上均有研究，且所研究的大多数病变为滤泡样，这一事实确立了GDF-15不仅是诊断滤泡上皮恶性甲状腺肿瘤的潜在标志物，也是区分甲状腺滤泡样良性和恶性肿瘤的潜在标志物。
