Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
Indian J Med Res. 2009 Nov;130(5):526-32.
BACKGROUND & OBJECTIVE: Association of Epstein-Barr virus (EBV) with Hodgkin lymphoma (HL) is particularly high in low-income countries, and resistance to apoptosis might play a role in pathogenesis and survival. Data from previous studies are not consistent, and none is available in children. Thus this study was undertaken on Indian children with classical Hodgkin lymphoma to assess the significance of bcl-2, bak and p53 expression, and apoptotic index in relation with EBV status and treatment outcome with chemotherapy alone.
Children (age<15 yr) with classical HL (n=143) were included in the study. Bcl-2, bak, p53, Ki67 and latent membrane protein-1 (LMP1) were detected by immunohistochemistry in pre-treatment lymph node biopsies. Apoptotic index was assessed by TdT-dUTP nick-end labelling (TUNEL).
Bcl-2, bak, p53 were expressed above positivity threshold in 83.3, 94.0 and 7.1 per cent of the cases respectively. More than 10 per cent of apoptotic tumour cells were seen in 60.4 per cent of the cases. 131 (91.6%) cases were EBV associated. EBV-positive cases had a significantly lower mean bak expression (p=0.001) and a lower apoptotic index, without higher proliferation index. Advanced stage showed a borderline association with bcl-2 expression in >25 per cent of tumour cells and p53 negative tumours. In univariate analysis, p53 positive cases, which were significantly associated with B symptoms, had a poorer overall survival (P=0.03) while low proliferation index was associated with poorer failure-free survival. Neither EBV status nor any of the apoptotic parameters studied showed independent association with survival.
INTERPRETATION & CONCLUSION: EBV detection in children with classical Hodgkin lymphoma was associated with significant lower bak expression and with lower spontaneous apoptosis of H-RS cells suggesting that EBV-LMP1 might downregulate bak pro-apoptotic protein. this needs to be substantiated further.
在低收入国家，爱泼斯坦-巴尔病毒（EBV）与霍奇金淋巴瘤（HL）的关联尤其高，而抗细胞凋亡可能在发病机制和生存中起作用。来自先前研究的数据并不一致，且在儿童中尚无相关数据。因此，本研究在印度患有经典霍奇金淋巴瘤的儿童中进行，以评估 bcl-2、bak 和 p53 表达以及凋亡指数与 EBV 状态的关系，并评估单独化疗治疗的结果。
本研究纳入了 143 例经典 HL 儿童患者。在治疗前的淋巴结活检中，通过免疫组织化学检测 bcl-2、bak、p53、Ki67 和潜伏膜蛋白 1（LMP1）的表达。通过 TdT-dUTP 缺口末端标记法（TUNEL）评估凋亡指数。
83.3%、94.0%和 7.1%的病例中 bcl-2、bak 和 p53 的表达均超过阳性阈值。60.4%的病例中可见超过 10%的凋亡肿瘤细胞。131 例（91.6%）为 EBV 相关病例。EBV 阳性病例的 bak 表达均值显著较低（p=0.001），凋亡指数较低，而增殖指数无升高。晚期病例与>25%肿瘤细胞中 bcl-2 表达以及 p53 阴性肿瘤的表达呈临界相关。在单变量分析中，与 B 症状显著相关的 p53 阳性病例的总生存率较差（P=0.03），而低增殖指数与无失败生存相关。EBV 状态或研究中任何凋亡参数均与生存无独立相关性。
在患有经典霍奇金淋巴瘤的儿童中检测到 EBV 与显著较低的 bak 表达和霍奇金-里斯细胞的自发性凋亡降低相关，这提示 EBV-LMP1 可能下调 bak 促凋亡蛋白。这需要进一步证实。
