title: bcl-2 protein is strongly expressed in post-transplant lymphoproliferative disorders.
abstract: 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.
authors.affiliation: University Department of Cellular Science, University of Oxford, U.K.
authors.forename: R
authors.initials: R
authors.lastname: Chetty
authors.forename: S
authors.initials: S
authors.lastname: Biddolph
authors.forename: L
authors.initials: L
authors.lastname: Kaklamanis
authors.forename: N
authors.initials: N
authors.lastname: Cary
authors.forename: S
authors.initials: S
authors.lastname: Stewart
authors.forename: A
authors.initials: A
authors.lastname: Giatromanolaki
authors.forename: K
authors.initials: K
authors.lastname: Gatter
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D016027:Heart Transplantation; D016041:Heart-Lung Transplantation; D006566:Herpesviridae Infections / Q000150:complications; D004854:Herpesvirus 4, Human; D006801:Humans; D016867:Immunocompromised Host; D016030:Kidney Transplantation; D008232:Lymphoproliferative Disorders / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D011183:Postoperative Complications / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014412:Tumor Virus Infections / Q000150:complications; D014763:Viral Matrix Proteins / Q000378:metabolism*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D014763:Viral Matrix Proteins