Juhlin C C
Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden.
Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden.
Scand J Surg. 2020 Sep;109(3):187-192. doi: 10.1177/1457496919850434. Epub 2019 May 26.
Endocrine surgeons and pathologists alike are well aware of the diagnostic predicament that follicular thyroid tumors impose in the clinical setting, best exemplified by the current inability to preoperatively assess the malignant potential of each individual lesion. As the proper recognition of a follicular thyroid carcinoma lies in the histopathological identification of invasive behavior, preoperative cytology alone is not yet sufficient to identify malignant tumors eligible for a total thyroidectomy upfront. Numerous auxiliary markers have been proposed as discriminating markers between follicular thyroid carcinomas and follicular thyroid adenomas, although many have proven suboptimal in terms of sensitivity, specificity, or overall clinical practicality. Of late, recurrent promoter mutations in the gene have been intimately coupled to subsets of well-differentiated thyroid cancer specimen with aggressive clinical characteristics as well as less differentiated forms of thyroid cancer with exceedingly poor prognosis. The mutations are thought to enhance the gene expressional output and cause immortalization through -associated mechanisms.
In this review, the current value of promoter mutations is detailed from a clinical angle-as well as the possible future application of additional gene aberrations as adjunct markers for the proper recognition of malignant potential.
promoter mutations are found in subsets of follicular thyroid carcinomas and follicular tumors of uncertain malignant potential while exceedingly rare in recurrence-free follicular thyroid adenomas. Collectively, these aberrancies are suggested as possible diagnostic and prognostic discriminators of follicular thyroid tumors.
gene analyses greatly facilitate the clinical assessment of follicular thyroid tumors, and pinpoints cases at risk of future recurrences. High-volume, tertiary thyroid centers are therefore recommended to implement the mutational screening in clinical routine.
内分泌外科医生和病理学家都清楚滤泡性甲状腺肿瘤在临床诊断中所带来的困境，目前无法在术前评估每个病变的恶性潜能就是最好的例证。由于滤泡性甲状腺癌的正确诊断依赖于侵袭行为的组织病理学鉴定，仅术前细胞学检查尚不足以识别适合直接进行全甲状腺切除术的恶性肿瘤。尽管许多辅助标志物在敏感性、特异性或整体临床实用性方面已被证明并不理想，但仍有众多辅助标志物被提议作为滤泡性甲状腺癌和滤泡性腺瘤之间的鉴别标志物。最近，该基因的复发性启动子突变与具有侵袭性临床特征的高分化甲状腺癌标本亚群以及预后极差的低分化甲状腺癌形式密切相关。这些突变被认为会增强该基因的表达输出，并通过相关机制导致细胞永生化。
在本综述中，从临床角度详细阐述了启动子突变的当前价值，以及其他基因异常作为辅助标志物在正确识别恶性潜能方面可能的未来应用。
在滤泡性甲状腺癌和恶性潜能不确定的滤泡性肿瘤亚群中发现了启动子突变，而在无复发的滤泡性腺瘤中极为罕见。总体而言，这些异常被认为可能是滤泡性甲状腺肿瘤的诊断和预后鉴别指标。
基因分析极大地促进了滤泡性甲状腺肿瘤的临床评估，并能确定有未来复发风险的病例。因此，建议大型三级甲状腺中心在临床常规中开展突变筛查。
