Naresh K N, Johnson J, Srinivas V, Soman C S, Saikia T, Advani S H, Badwe R A, Dinshaw K A, Muckaden M, Magrath I, Bhatia K
Department of Pathology, Tata Memorial Hospital, Mumbai, India.
Ann Oncol. 2000 Jan;11(1):91-6. doi: 10.1023/a:1008337100424.
Most Epstein-Barr virus (EBV) associated lymphoproliferative disorders have high proliferation indices. However, classical Hodgkin's disease (cHD) is heterogeneous, with respect to proliferation index of the Reed-Sternberg cell (RS cell), and EBV association. Hence, we investigated whether cHD with and without EBV-association differ with respect to the proliferation index of the RS cells. Further we investigated whether this would have a bearing on patients survival.
We investigated 110 cases of cHD for: a) EBV association by immunohistochemical demonstration of EBV-latent membrane protein-1 and EBV encoded nuclear RNA 1 by mRNA in situ hybridisation; b) Proliferating cell nuclear antigen (PCNA) expression in the RS cells.
EBV association was noted in 86 of 110 cases (78%). Higher PCNA expression (P = 0.004) and younger age (P = 0.001) correlated independently with EBV association. The 10 year relapse free survival (RFS) of EBV+ and EBV- patients were 60% and 44%, respectively (P = 0.03). The 10 year overall survival (OS) of EBV+ and EBV- patients were 85% and 64%, respectively (P = 0.03). EBV association maintained its significant impact on RFS and OS within Cox proportional hazard model.
Our study suggests that EBV is likely to confer a higher PCNA expression and also contribute towards maintaining the RS cells of cHD in cell cycle. Hence, RS cells in EBV associated cHD would be more responsive to chemotherapy and radiotherapy associated DNA damage. Thus, EBV-association provides survival advantage to cHD patients treated with standard chemotherapy and radiotherapy protocols.
大多数与爱泼斯坦-巴尔病毒（EBV）相关的淋巴增殖性疾病具有较高的增殖指数。然而，经典型霍奇金淋巴瘤（cHD）在里德-斯腾伯格细胞（RS细胞）的增殖指数以及EBV关联方面具有异质性。因此，我们研究了伴有和不伴有EBV关联的cHD在RS细胞增殖指数方面是否存在差异。此外，我们还研究了这是否会对患者的生存产生影响。
我们对110例cHD患者进行了以下研究：a）通过免疫组织化学检测EBV潜伏膜蛋白-1以及采用mRNA原位杂交检测EBV编码的核RNA 1来确定EBV关联情况；b）检测RS细胞中增殖细胞核抗原（PCNA）的表达。
110例病例中有86例（78%）存在EBV关联。较高的PCNA表达（P = 0.004）和较年轻的年龄（P = 0.001）与EBV关联独立相关。EBV阳性和EBV阴性患者的10年无复发生存率（RFS）分别为60%和44%（P = 0.03）。EBV阳性和EBV阴性患者的10年总生存率（OS）分别为85%和64%（P = 0.03）。在Cox比例风险模型中，EBV关联对RFS和OS仍具有显著影响。
我们的研究表明，EBV可能导致较高的PCNA表达，并且有助于使cHD的RS细胞维持在细胞周期中。因此，EBV相关cHD中的RS细胞对化疗和放疗相关的DNA损伤更敏感。所以，EBV关联为接受标准化疗和放疗方案治疗的cHD患者提供了生存优势。
