Labrecque L G, Xue S A, Kazembe P, Phillips J, Lampert I, Wedderburn N, Griffin B E
Department of Infectious Diseases (Virology), Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Int J Cancer. 1999 Mar 31;81(1):6-11. doi: 10.1002/(sici)1097-0215(19990331)81:1<6::aid-ijc2>3.0.co;2-2.
A study on the Epstein-Barr virus (EBV)-associated malignancy (endemic) Burkitt's lymphoma (BL) was initiated on fine-needle-aspiration biopsies from 46 proven BL cases in Malawi. Gene expression that might correlate with patient serology (where high levels of antibodies to lytically related genes are commonly observed) was explored. In two-thirds of the cases, we identified the EBV BZLF1 replication activator intermediate early protein ZEBRA in varying quantities and to varying extents in cells by immuno-cytochemistry. The early lytic-cycle gene transcript BHLF1 was assessed positively by solid-phase hybridisation in over half of the same tumours. Evidence of transcription of these genes was confirmed on a smaller number of surgically removed fresh biopsies by RT-PCR. We asked whether our findings, which are generally counter to the established notion that EBV gene expression in BLs is restricted to the latent function, EBNA1, might offer some explanation for the differential responses to chemotherapy observed among African patients. Where the duration of follow-up was sufficient to assign the cases (37 in number) to one of 3 categories, namely, complete, partial or no response, a significant correlation between expression of the viral function ZEBRA and a positive patient response to treatment was found. Lack of this was associated with poor prognosis. Clinical data and EBV gene expression results support the postulate of subgroups of African BLs, the intermediate early antigen providing a marker of potential use in patient management.
一项关于爱泼斯坦-巴尔病毒（EBV）相关恶性肿瘤（地方性）伯基特淋巴瘤（BL）的研究，始于对马拉维46例经证实的BL病例进行细针穿刺活检。探索了可能与患者血清学相关的基因表达（通常观察到针对裂解相关基因的高水平抗体）。在三分之二的病例中，我们通过免疫细胞化学在细胞中鉴定出数量和程度各异的EBV BZLF1复制激活剂早期蛋白ZEBRA。在超过半数的同一肿瘤中，通过固相杂交对早期裂解周期基因转录本BHLF1进行了阳性评估。通过逆转录聚合酶链反应（RT-PCR）在少量手术切除的新鲜活检组织上证实了这些基因的转录证据。我们想知道，我们的发现通常与已确立的观点相反，即BL中的EBV基因表达仅限于潜伏功能EBNA1，这是否可以为非洲患者中观察到的化疗差异反应提供一些解释。在随访时间足以将病例（共37例）分为完全缓解、部分缓解或无反应这3类之一的情况下，发现病毒功能ZEBRA的表达与患者对治疗的阳性反应之间存在显著相关性。缺乏这种相关性与预后不良相关。临床数据和EBV基因表达结果支持非洲BL亚组的假设，即早期抗原可为患者管理提供潜在有用的标志物。
