Etzel Barbara-Magdalena, Gerth Melanie, Chen Yuan, Wünsche Elisa, Facklam Tina, Beck James F, Guntinas-Lichius Orlando, Petersen Iver
Institute of Pathology, Jena University Hospital, Jena, Germany.
Children's Clinic, Department of Pediatric Hematology and Oncology, Jena University Hospital, Jena, Germany.
Pathol Res Pract. 2017 Mar;213(3):256-260. doi: 10.1016/j.prp.2016.11.001. Epub 2016 Nov 26.
Survival and proliferation of Hodgkin and Reed-Sternberg (HRS) cells, the malignant cells of classical Hodgkin lymphoma (CHL), are dependent on constitutive activation of nuclear factor kB (NF-κB). A20, encoded by TNF alpha-induced protein 3 (TNFAIP, one of the inhibitors of NF-kB, was found to be inactivated by deletions and/or point mutations in CHL.
TNFAIP mutations were examined in 37 patients with CHL by using PCR and direct sequencing. In addition, protein expression of A20 was evaluated by immunohistochemistry. Epstein-Barr virus (EBV) status of HL samples was determined by EBV EBER chromogenic in situ hybridization (ISH).
We identified 8 mutation positive cases in a collective of 37 investigated cases (22%). Mutations were most frequent in the nodular sclerosis subtype. Our results revealed the tendency that cases harboring A20 mutations were negative for A20 staining. None of A20 mutation-positive CHL cases showed EBV infection.
Our study confirms the involvement of the TNFAIP tumor suppressor gene in CHL. A20 may represent a suppressor of human lymphoma and provide a critical molecular link between chronic inflammation and cancer. None of A20 mutation-positive CHL cases showed EBV infection. This fact suggests complementing functions of TNFAIP inactivation and EBV infection in CHL pathogenesis and may represent an interesting point of further investigations.
霍奇金和里德-斯腾伯格（HRS）细胞是经典型霍奇金淋巴瘤（CHL）的恶性细胞，其存活和增殖依赖于核因子κB（NF-κB）的组成性激活。由肿瘤坏死因子α诱导蛋白3（TNFAIP3，NF-κB的抑制剂之一）编码的A20，在CHL中被发现因缺失和/或点突变而失活。
采用聚合酶链反应（PCR）和直接测序法检测37例CHL患者的TNFAIP3突变情况。此外，通过免疫组织化学评估A20的蛋白表达。采用EBV EBER显色原位杂交（ISH）法确定HL样本的爱泼斯坦-巴尔病毒（EBV）状态。
在37例被调查病例中，我们鉴定出8例突变阳性病例（22%）。突变在结节硬化亚型中最为常见。我们的结果显示出携带A20突变的病例A20染色呈阴性的趋势。A20突变阳性的CHL病例均未显示EBV感染。
我们的研究证实了TNFAIP3肿瘤抑制基因参与CHL的发生。A20可能是人类淋巴瘤的一种抑制因子，并在慢性炎症与癌症之间提供关键的分子联系。A20突变阳性的CHL病例均未显示EBV感染。这一事实表明TNFAIP3失活和EBV感染在CHL发病机制中具有互补功能，可能是进一步研究的一个有趣点。
