Insilla Andrea Cacciato, Proietti Agnese, Borrelli Nicla, Macerola Elisabetta, Niccoli Cristina, Vitti Paolo, Miccoli Paolo, Basolo Fulvio
Department of Surgical Pathology, University Hospital of Pisa, I-56126 Pisa, Italy.
Department of Endocrinology, University Hospital of Pisa, I-56126 Pisa, Italy.
Oncol Lett. 2018 Mar;15(3):2763-2770. doi: 10.3892/ol.2017.7675. Epub 2017 Dec 21.
Papillary thyroid carcinoma (PTC) is the most common type of endocrine malignancy and accounts for ~80% of thyroid carcinomas in adults and 90% in children. Risk stratification is important for identifying patients at higher risk and, for this reason, recent advances in molecular genetics of thyroid cancer can be applied to provide novel biomarkers useful in understanding tumor behavior. B-Raf proto-oncogene, serine/threonine kinase (BRAF) and rat sarcoma (RAS) mutations have been widely studied and appear to have an important role in thyroid tumorigenesis. Somatic telomerase reverse transcriptase (TERT) promoter mutations have been recently identified in several types of malignant tumors, including thyroid neoplasia; however, the actual role of TERT mutations in thyroid tumorigenesis is still under debate. In the present study, the mutational status of BRAF, RAS and TERT was analyzed in order to elucidate the roles of these genes in thyroid tumorigenesis. The TERT mutational analysis was also correlated with an immunohistochemical study of TERT protein expression. According to the literature, our data provide evidence of the BRAF and RAS roles in thyroid tumorigenesis, supporting an association between BRAF (V600E) mutations and the more aggressive clinical and pathological features of thyroid tumors. By contrast, TERT mutations were not significantly associated with any clinical parameters; therefore, its role in initial tumorigenesis should be further investigated.
甲状腺乳头状癌（PTC）是最常见的内分泌恶性肿瘤类型，约占成人甲状腺癌的80%，儿童甲状腺癌的90%。风险分层对于识别高危患者很重要，因此，甲状腺癌分子遗传学的最新进展可用于提供有助于理解肿瘤行为的新型生物标志物。B-Raf原癌基因、丝氨酸/苏氨酸激酶（BRAF）和大鼠肉瘤（RAS）突变已得到广泛研究，似乎在甲状腺肿瘤发生中起重要作用。体细胞端粒酶逆转录酶（TERT）启动子突变最近在包括甲状腺肿瘤在内的几种恶性肿瘤中被发现；然而，TERT突变在甲状腺肿瘤发生中的实际作用仍存在争议。在本研究中，分析了BRAF、RAS和TERT的突变状态，以阐明这些基因在甲状腺肿瘤发生中的作用。TERT突变分析还与TERT蛋白表达的免疫组织化学研究相关。根据文献，我们的数据提供了BRAF和RAS在甲状腺肿瘤发生中作用的证据，支持BRAF（V600E）突变与甲状腺肿瘤更具侵袭性的临床和病理特征之间的关联。相比之下，TERT突变与任何临床参数均无显著相关性；因此，其在肿瘤初始发生中的作用应进一步研究。
