Department of Molecular Pathology, Ehime University Graduate School of Medicine , Shitsukawa, Toon City, Ehime 791-0295, Japan.
Acta Histochem Cytochem. 2014 Jun 28;47(3):125-31. doi: 10.1267/ahc.14012. Epub 2014 Jun 26.
Analysis of archival formalin-fixed, paraffin-embedded (FFPE) pathological specimens of three case of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) and three cases of classical Hodgkin lymphoma (CHL) revealed that hypermethylation of the BOB.1 gene promoter was exclusively observed in CHL. A discrepancy was observed, however, between the methylation status of the BOB.1 gene promoter and its expression in the EBV-positive mixed cellular CHL (MCCHL). Since MCCHL lacks the typical B-cell phenotype even in the presence of abundant BOB.1 transcription factors, functional activity of BOB.1 may be lost or reduced by a mechanism other than epigenetic gene silencing. When some tumor-suppressor gene products have lost their biological function, impact or significance of derepression of such genes may be little. Therefore, when interpreting immunohistochemical results for diagnostic or research purposes, it must be borne in mind that apparent positive immunostaining can merely be the result of chromatin remodeling and that such transient expression often has little functional significance. Any apparent positive immunohistochemical result needs to be interpreted carefully with the help of the hypermethylation status as a molecular marker of gene silencing memory.
分析三例 EBV 阳性弥漫性大 B 细胞淋巴瘤 (DLBCL) 和三例经典霍奇金淋巴瘤 (CHL) 的存档福尔马林固定、石蜡包埋 (FFPE) 病理标本显示，BOB.1 基因启动子的高甲基化仅在 CHL 中观察到。然而，在 EBV 阳性混合细胞 CHL (MCCHL) 中，BOB.1 基因启动子的甲基化状态与其表达之间存在差异。由于 MCCHL 甚至在存在大量 BOB.1 转录因子的情况下缺乏典型的 B 细胞表型，因此 BOB.1 的功能活性可能通过除表观遗传基因沉默之外的机制丢失或减少。当一些肿瘤抑制基因产物失去其生物学功能时，这些基因去抑制的影响或意义可能很小。因此，在为诊断或研究目的解释免疫组织化学结果时，必须记住，明显的阳性免疫染色仅仅可能是染色质重塑的结果，并且这种瞬时表达通常没有什么功能意义。任何明显的阳性免疫组织化学结果都需要借助甲基化状态作为基因沉默记忆的分子标志物进行仔细解释。
