Chang Kung-Chao, Chang Yao, Jones Dan, Su Ih-Jen
Department of Pathology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Am J Clin Pathol. 2009 Jul;132(1):50-9. doi: 10.1309/AJCPBDFR5L5UOAUZ.
Reed-Sternberg (RS) cells represent a histopathologic hallmark for Hodgkin lymphoma (HL). Viral proteins may induce aberrant expression of cyclin A and lead to multinucleation in virus-infected cells. We investigated whether Epstein-Barr virus (EBV) latent membrane protein-1 (LMP1) and cyclin A are involved in the morphogenesis of RS cells. We immunohistochemically analyzed "individual" tumor cells in 34 HLs for the subcellular expression of cyclin A and HL-related markers. In LMP1+ and LMP1- HLs, multinucleated RS cells aberrantly expressed cyclin A in cytoplasm, while the mononuclear Hodgkin cells expressed cyclin A predominantly in nuclei (P < .001). No differential expression of CD15, CD30, or CD99 in HL cells was found. In vitro, EBV-LMP1 increased cytoplasmic cyclin A expression and multinucleation in an HL cell line. Therefore, the aberrant expression of cyclin A is commonly associated with RS cell morphologic features in HL, probably through LMP1 signaling or other similar mechanisms in EBV- cases.
里德-施特恩伯格（RS）细胞是霍奇金淋巴瘤（HL）的组织病理学标志。病毒蛋白可能诱导细胞周期蛋白A异常表达，并导致病毒感染细胞出现多核化。我们研究了爱泼斯坦-巴尔病毒（EBV）潜伏膜蛋白1（LMP1）和细胞周期蛋白A是否参与RS细胞的形态发生。我们对34例HL中的“单个”肿瘤细胞进行免疫组织化学分析，以检测细胞周期蛋白A和HL相关标志物的亚细胞表达情况。在LMP1阳性和LMP1阴性的HL中，多核RS细胞在细胞质中异常表达细胞周期蛋白A，而单核霍奇金细胞则主要在细胞核中表达细胞周期蛋白A（P <.001）。未发现HL细胞中CD15、CD30或CD99有差异表达。在体外，EBV-LMP1可增加HL细胞系中细胞质细胞周期蛋白A的表达和多核化。因此，细胞周期蛋白A的异常表达通常与HL中RS细胞的形态学特征相关，可能是通过LMP1信号传导或EBV阴性病例中的其他类似机制。
