Fumarate Hydratase Mutations and Alterations in Leiomyoma With Bizarre Nuclei.
Fumarate Hydratase Mutations and Alterations in Leiomyoma With Bizarre Nuclei.
复制标题
具有奇异细胞核的平滑肌瘤中的富马酸水合酶突变和改变。
DOI：
10.1097/pgp.0000000000000447
复制
发表时间：
2018-09
期刊：
影响因子：
--
通讯作者：
Wei JJ
中科院分区：
文献类型：
--
作者：
Zhang Q;Poropatich K;Ubago J;Xie J;Xu X;Frizzell N;Kim J;Kong B;Wei JJ
奇异核平滑肌瘤是一种具有不典型组织学特征的子宫平滑肌肿瘤。虽然一些LM-BN与平滑肌肉瘤（LMS）有几个显著的遗传改变，包括p16和p53，但LM-BN的潜在肿瘤发生仍然很大程度上未知。如我们以前所报道的，LM-BN可根据不同的核特征分为两种亚型，I型和II型。I型LM-BN具有与具有富马酸水合酶（FH）改变的子宫平滑肌肿瘤相似的组织学特征。在这项研究中，我们研究了FH表达和FH突变77例LM-BN（40例I型病例和37例II型病例）。使用S-（2-琥珀酰基）-半胱氨酸抗体（2SC，一种与FH失活和随后富马酸盐蓄积相关的蛋白质修饰）和FH抗体（富马酸水合酶基因产物）通过免疫组织化学（IHC）检查FH表达。对72例LM-BN肿瘤进行桑格测序以检测FH突变。我们发现51%（39/77）的LM-BN在2SC和FH的免疫组化检测中显示FH改变。突变分析显示21%（15/72）的LM-BN携带FH基因突变。进一步分析显示，85%（34/40）的FH改变是I型LM-BN，而19%（7/37）是II型LM-BN。我们的研究结果表明，超过一半的组织学诊断LM-BN可能与FH改变或FH突变，其中大多数具有I型LM-BN的组织学特征。
Leiomyoma with bizarre nuclei (LM-BN), is a variant of uterine smooth muscle tumor with atypical histological features. Although some LM-BN share several significant genetic alterations with leiomyosarcoma (LMS), including p16 and p53, the underlying tumorigenesis of LM-BN remains largely unknown. As we previous reported, LM-BN can be divided into two subtypes, type I and type II, based on different nuclear features. Type I LM-BN have similar histologic features as uterine smooth muscle tumors with fumarate hydratase (FH) alterations. In this study, we examined FH expression and FH mutations in 77 LM-BN (40 type I cases and 37 type II cases). FH expression was examined by immunohistochemistry (IHC) using S-(2-succino)-cysteine antibodies (2SC, a protein modification associated with FH inactivation and subsequent fumarate accumulation) and FH antibodies (fumarate hydratase gene products). Seventy-two LM-BN tumors underwent Sanger sequencing to detect FH mutations. We found that 51% (39/77) of LM-BN showed FH alterations detected by immunohistochemistry with both 2SC and FH. Mutational analysis showed that 21% (15/72) of LM-BN harbored FH gene mutations. Further analysis revealed that 85% (34/40) of those with FH alterations were type I LM-BN while 19% (7/37) were type II LM-BN. Our findings suggest that over half of histologically-diagnosed LM-BN may be related to FH alterations or FH mutations and the majority of these have the characteristic histologic features of type I LM-BN.