TRAF7 mutations and immunohistochemical study of uterine adenomatoid tumor compared with malignant mesothelioma
TRAF7 mutations and immunohistochemical study of uterine adenomatoid tumor compared with malignant mesothelioma
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DOI：
10.1016/j.humpath.2021.02.007
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发表时间：
2021-03-27
期刊：
影响因子：
3.3
通讯作者：
Ohbayashi, Chiho
中科院分区：
文献类型：
--
作者：
Itami, Hiroe;Fujii, Tomomi;Ohbayashi, Chiho
腺瘤样瘤（AT）是一种预后良好的良性间皮瘤，通常发生在女性和男性生殖道，包括子宫。AT在遗传上由肿瘤坏死因子受体相关因子（TRAF）7突变定义，大量AT病例显示免疫抑制。另一方面，恶性间皮瘤（malignant mesotheliomas，简称MM）是一种预后极差的恶性间皮瘤。通过基因序列分析或免疫组化方法比较了来自子宫和胸膜或腹膜来源的AT中TRAF、甲硫腺苷磷酸化酶（MTAP）和BRCA相关核蛋白1（BAP 1）的遗传改变。来自患者的福尔马林固定石蜡包埋组织用于51例子宫AT病例和34例胸膜或腹膜MM病例的L1细胞粘附分子（L1 CAM）、BAP 1、MTAP和唾液酸化蛋白HEG同源物1（HEG 1）的免疫组化染色，并用于44例AT病例和21例MM病例的TRAF 7基因的下一代测序。ATs的L1 CAM表达率显著高于ATs，而ATs的MTAP和BAP 1表达缺失率显著高于ATs。肿瘤类型之间的HEG 1表达率无差异。大多数AT（37/44; 84%）在TRAF 7中具有体细胞突变，但没有一个AT在TRAF 7中具有体细胞突变（0/21; 0%）。此外，少量AT病例与免疫抑制史相关（9/51; 17.6%）。TRAF 7突变是区别AT与MM的主要因素之一，大多数AT病例可能与免疫抑制无关。(C)2021爱思唯尔公司All rights reserved.
Adenomatoid tumors (ATs) are benign mesothelial tumors with a good prognosis and usually occur in female and male genital tracts, including in the uterus. ATs are genetically defined by tumor necrosis factor receptor-associated factor (TRAF) 7 mutations, and a high number of AT cases show immunosuppression. On the other hand, malignant mesotheliomas (MMs) are malignant mesothelial tumors with a very poor prognosis. Genetic alterations in TRAF, methylthioadenosine phosphorylase(MTAP), and BRCA-associated nuclear protein 1 (BAP1) in ATs derived from the uterus and MMs of pleural or peritoneal origin were compared by gene sequence analysis or immunohistochemical approaches. Formalin-fixed paraffin-embedded tissues derived from patients were used for immunohistochemical staining of L1 cell adhesion molecule (L1CAM), BAP1, MTAP, and sialylated protein HEG homolog 1 (HEG1) in 51 uterine AT cases and 34 pleural or peritoneal MM cases and for next-generation sequencing of the TRAF7 gene in 44 AT cases and 21 MM cases. ATs had a significantly higher rate of L1CAM expression than MMs, whereas MMs had a significantly higher rate of loss of MTAP and BAP1 expression than ATs. There was no difference in the rate of HEG1 expression between the tumor types. Most of the ATs (37/44; 84%) had somatic mutations in TRAF7, but none of the MMs had somatic mutations in TRAF7 (0/21; 0%). In addition, a low number of AT cases were associated with a history of immunosuppression (9/51; 17.6%). TRAF7 mutation is one of the major factors distinguishing the development of AT from MM, and immunosuppression might not be associated with most AT cases. (C) 2021 Elsevier Inc. All rights reserved.