Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
Fondazione Italiana per la Ricerca sulle Malattie dell'Osso (F.I.R.M.O.) Italian Foundation for the Research on Bone Diseases, Florence, Italy.
Front Endocrinol (Lausanne). 2022 Feb 24;13:834362. doi: 10.3389/fendo.2022.834362. eCollection 2022.
Parathyroid carcinoma (PC) is an extremely rare malignancy, accounting less than 1% of all parathyroid neoplasms, and an uncommon cause of primary hyperparathyroidism (PHPT), characterized by an excessive secretion of parathyroid hormone (PTH) and severe hypercalcemia. As opposed to parathyroid hyperplasia and adenomas, PC is associated with a poor prognosis, due to a commonly unmanageable hypercalcemia, which accounts for death in the majority of cases, and an overall survival rate of 78-85% and 49-70% at 5 and 10 years after diagnosis, respectively. No definitively effective therapies for PC are currently available. The mainly employed treatment for PC is the surgical removal of tumoral gland(s). Post-surgical persistent or recurrent disease manifest in about 50% of patients. The comprehension of genetic and epigenetic bases and molecular pathways that characterize parathyroid carcinogenesis is important to distinguish malignant PCs from benign adenomas, and to identify specific targets for novel therapies. Germline heterozygote inactivating mutations of the tumor suppressor gene, with somatic loss of heterozygosity at 1q31.2 locus, account for about 50-75% of familial cases; over 75% of sporadic PCs harbor biallelic somatic inactivation/loss of . Recurrent mutations of the gene, a recurrent mutation in the gene, genetic amplification of the gene, alterations of the PI3K/AKT/mTOR signaling pathway, and modifications of microRNA expression profile and gene promoter methylation pattern have all been detected in PC. Here, we review the current knowledge on gene mutations and epigenetic changes that have been associated with the development of PC, in both familial and sporadic forms of this malignancy.
甲状旁腺癌（PC）是一种极其罕见的恶性肿瘤，占所有甲状旁腺肿瘤的比例不到 1%，也是原发性甲状旁腺功能亢进症（PHPT）的不常见病因，其特征为甲状旁腺激素（PTH）过度分泌和严重高钙血症。与甲状旁腺增生和腺瘤不同，PC 预后较差，由于常难以控制的高钙血症，导致大多数病例死亡，诊断后 5 年和 10 年的总生存率分别为 78-85%和 49-70%。目前尚无针对 PC 的明确有效治疗方法。PC 的主要治疗方法是手术切除肿瘤腺体。术后持续性或复发性疾病约见于 50%的患者。了解导致甲状旁腺癌发生的遗传和表观遗传基础以及分子途径对于将恶性 PC 与良性腺瘤区分开来，并确定新疗法的特定靶点非常重要。肿瘤抑制基因的种系杂合失活突变，伴有 1q31.2 位点的杂合性丢失，约占家族性病例的 50-75%；超过 75%的散发性 PC 存在双等位基因体细胞失活/丢失。基因的复发性突变、基因的复发性突变、基因的遗传扩增、PI3K/AKT/mTOR 信号通路的改变以及 microRNA 表达谱和基因启动子甲基化模式的修饰均已在 PC 中检测到。在这里，我们综述了与这种恶性肿瘤的家族性和散发性形式相关的基因突变和表观遗传变化的最新知识。
