Chetty R, Biddolph S, Kaklamanis L, Cary N, Stewart S, Giatromanolaki A, Gatter K
University Department of Cellular Science, University of Oxford, U.K.
J Pathol. 1996 Nov;180(3):254-8. doi: 10.1002/(SICI)1096-9896(199611)180:3<254::AID-PATH671>3.0.CO;2-D.
The aim of this study was to examine a series of Epstein-Barr virus (EBV)-driven post-transplant lymphoproliferative disorder (PTLDs), in order to ascertain the level of bcl-2 immunostaining; to explore the relationship between bcl-2 and p53 protein expression and to see if any correlation exists between bcl-2 and EBV-latent membrane protein 1 (LMP-1). Seventeen renal and 11 heart/heart-lung PTLD cases were stained with antibodies to EBV-LMP-1, bcl-2 and p53, using paraffin-embedded tissue. All cases of PTLD strong co-expressed bcl-2 and EBV-LMP. Positive staining was present in small lymphoid and larger immunoblastic cells. These two antibodies showed parallel staining intensity. p53 expression was noted in 13 of 17 renal PTLDs, but in ten of the positive cases only 5-10 per cent of cells were stained. Seven of the 11 heart/heart-lung cases showed 50-60 per cent of cells to be p53-positive; in the remaining for cases, 10-20 per cent of cells were positive. bcl-2 protein, as detected by immunohistochemistry, is markedly overexpressed in all case of PTLD. This study also demonstrates a strongly positive correlation between bcl-2 expression and EBV-LMP-1 detection in PTLD. An inverse pattern of p53 and bcl-2 immunoexpression is noted in PTLDs with "high grade' histology: these show marked expression of bcl-2, while p53 is downregulated. A Fisher's exact test yielded a P value of 0-12 when comparing p53-positive renal PTLDs with p53-positive heart/heart-lung PTLDs, indicating that any difference seen is not statistically significant. The postulated mechanism for the positive correlation between bcl-2 and EBV-LMP-1 is that EBV upregulates bcl-2, either directly or indirectly, thus promoting cell survival and ultimately successful viral replication.
本研究旨在检测一系列爱泼斯坦-巴尔病毒（EBV）驱动的移植后淋巴组织增生性疾病（PTLD），以确定bcl-2免疫染色水平；探讨bcl-2与p53蛋白表达之间的关系，并观察bcl-2与EBV潜伏膜蛋白1（LMP-1）之间是否存在相关性。使用石蜡包埋组织，对17例肾移植后淋巴组织增生性疾病和11例心脏/心肺移植后淋巴组织增生性疾病病例进行EBV-LMP-1、bcl-2和p53抗体染色。所有PTLD病例均强烈共表达bcl-2和EBV-LMP。在小淋巴细胞和较大的免疫母细胞中出现阳性染色。这两种抗体显示出平行的染色强度。17例肾移植后淋巴组织增生性疾病中有13例检测到p53表达，但在10例阳性病例中，仅5%-10%的细胞被染色。11例心脏/心肺移植后淋巴组织增生性疾病中有7例显示50%-60%的细胞p53呈阳性；在其余4例中，10%-20%的细胞呈阳性。通过免疫组织化学检测发现，bcl-2蛋白在所有PTLD病例中均明显过度表达。本研究还表明，在PTLD中，bcl-2表达与EBV-LMP-1检测之间存在强正相关。在具有“高级别”组织学的PTLD中，观察到p53和bcl-2免疫表达呈相反模式：这些病例显示bcl-2明显表达，而p53下调。将p53阳性的肾移植后淋巴组织增生性疾病与p53阳性的心脏/心肺移植后淋巴组织增生性疾病进行比较时，Fisher精确检验得出的P值为0.12，表明观察到的任何差异均无统计学意义。bcl-2与EBV-LMP-1之间正相关的假定机制是，EBV直接或间接上调bcl-2，从而促进细胞存活并最终实现病毒的成功复制。
