Abstract
AIMS--To evaluate whether there is any correlation between the expression of Epstein-Barr virus (EBV) latent membrane protein (LMP) and oncoprotein bcl-2 in the lymph node biopsy specimens of a Chinese patient with EBV-related reactive lymphoproliferation who later developed T cell lymphoma after a short period of time. METHODS--Immunohistochemistry, with a standard alkaline phosphatase antialkaline phosphatase (APAAP) method and New Fuchsin as a chromogen, was used for single staining of bcl-2 or LMP. Double immunostaining combining APAAP and indirect immunofluorescence was performed for dual labelling of LMP and bcl-2. RESULTS--bcl-2 was expressed in 10-30% of cells in the first lymph node biopsy specimen (EBV-associated lymphoproliferative disorder) and 30-50% of cells in the second lymph node biopsy specimen (T cell lymphoma). LMP was expressed in the first biopsy specimen but not in the second. Double immunostaining results showed that around 78% of LMP positive cells were bcl-2 negative and 94% bcl-2 positive cells were LMP negative. Among the very small fraction of LMP and bcl-2 double positive cells, the intensity of bcl-2 staining was heterogeneous and was not always stronger than that observed in LMP negative bcl-2 positive cells. CONCLUSIONS--The expression of bcl-2 protein is independent of LMP protein status in vivo. Several mechanisms may be involved in EBV associated lymphomagenesis, and bcl-2 induction may occur independently of LMP expression.
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- Armstrong A. A., Gallagher A., Krajewski A. S., Jones D. B., Wilkins B. S., Onions D. E., Jarrett R. F. The expression of the EBV latent membrane protein (LMP-1) is independent of CD23 and bcl-2 in Reed-Sternberg cells in Hodgkin's disease. Histopathology. 1992 Jul;21(1):72–73. doi: 10.1111/j.1365-2559.1992.tb00346.x. [DOI] [PubMed] [Google Scholar]
- Finke J., Fritzen R., Ternes P., Trivedi P., Bross K. J., Lange W., Mertelsmann R., Dölken G. Expression of bcl-2 in Burkitt's lymphoma cell lines: induction by latent Epstein-Barr virus genes. Blood. 1992 Jul 15;80(2):459–469. [PubMed] [Google Scholar]
- Gregory C. D., Dive C., Henderson S., Smith C. A., Williams G. T., Gordon J., Rickinson A. B. Activation of Epstein-Barr virus latent genes protects human B cells from death by apoptosis. Nature. 1991 Feb 14;349(6310):612–614. doi: 10.1038/349612a0. [DOI] [PubMed] [Google Scholar]
- Hanto D. W., Gajl-Peczalska K. J., Frizzera G., Arthur D. C., Balfour H. H., Jr, McClain K., Simmons R. L., Najarian J. S. Epstein-Barr virus (EBV) induced polyclonal and monoclonal B-cell lymphoproliferative diseases occurring after renal transplantation. Clinical, pathologic, and virologic findings and implications for therapy. Ann Surg. 1983 Sep;198(3):356–369. doi: 10.1097/00000658-198309000-00012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Henderson S., Rowe M., Gregory C., Croom-Carter D., Wang F., Longnecker R., Kieff E., Rickinson A. Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell. 1991 Jun 28;65(7):1107–1115. doi: 10.1016/0092-8674(91)90007-l. [DOI] [PubMed] [Google Scholar]
- Herbst H., Steinbrecher E., Niedobitek G., Young L. S., Brooks L., Müller-Lantzsch N., Stein H. Distribution and phenotype of Epstein-Barr virus-harboring cells in Hodgkin's disease. Blood. 1992 Jul 15;80(2):484–491. [PubMed] [Google Scholar]
- Hockenbery D., Nuñez G., Milliman C., Schreiber R. D., Korsmeyer S. J. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 1990 Nov 22;348(6299):334–336. doi: 10.1038/348334a0. [DOI] [PubMed] [Google Scholar]
- Jiwa N. M., Kanavaros P., van der Valk P., Walboomers J. M., Horstman A., Vos W., Mullink H., Meijer C. J. Expression of c-myc and bcl-2 oncogene products in Reed-Sternberg cells independent of presence of Epstein-Barr virus. J Clin Pathol. 1993 Mar;46(3):211–217. doi: 10.1136/jcp.46.3.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kondo E., Nakamura S., Onoue H., Matsuo Y., Yoshino T., Aoki H., Hayashi K., Takahashi K., Minowada J., Nomura S. Detection of bcl-2 protein and bcl-2 messenger RNA in normal and neoplastic lymphoid tissues by immunohistochemistry and in situ hybridization. Blood. 1992 Oct 15;80(8):2044–2051. [PubMed] [Google Scholar]
- Lu Q. L., Elia G., Lucas S., Thomas J. A. Bcl-2 proto-oncogene expression in Epstein-Barr-virus-associated nasopharyngeal carcinoma. Int J Cancer. 1993 Jan 2;53(1):29–35. doi: 10.1002/ijc.2910530107. [DOI] [PubMed] [Google Scholar]
- Martin J. M., Veis D., Korsmeyer S. J., Sugden B. Latent membrane protein of Epstein-Barr virus induces cellular phenotypes independently of expression of Bcl-2. J Virol. 1993 Sep;67(9):5269–5278. doi: 10.1128/jvi.67.9.5269-5278.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pezzella F., Tse A. G., Cordell J. L., Pulford K. A., Gatter K. C., Mason D. Y. Expression of the bcl-2 oncogene protein is not specific for the 14;18 chromosomal translocation. Am J Pathol. 1990 Aug;137(2):225–232. [PMC free article] [PubMed] [Google Scholar]
- Ramshaw A. L., Parums D. V. Combined immunohistochemical and immunofluorescence method to determine the phenotype of proliferating cell populations. J Clin Pathol. 1992 Nov;45(11):1015–1017. doi: 10.1136/jcp.45.11.1015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sandvej K. B., Hamilton-Dutoit S. J., Pallesen G. Influence of Epstein-Barr virus encoded latent membrane protein 1 on the expression of CD23 antigen, ICAM-1 and LFA-3 in Hodgkin and Reed-Sternberg cells. A morphometric analysis. Leuk Lymphoma. 1993 Jan;9(1-2):95–101. doi: 10.3109/10428199309148510. [DOI] [PubMed] [Google Scholar]
- Thomas J. A., Hotchin N. A., Allday M. J., Amlot P., Rose M., Yacoub M., Crawford D. H. Immunohistology of Epstein-Barr virus-associated antigens in B cell disorders from immunocompromised individuals. Transplantation. 1990 May;49(5):944–953. doi: 10.1097/00007890-199005000-00022. [DOI] [PubMed] [Google Scholar]
- Weiss L. M., Warnke R. A., Sklar J., Cleary M. L. Molecular analysis of the t(14;18) chromosomal translocation in malignant lymphomas. N Engl J Med. 1987 Nov 5;317(19):1185–1189. doi: 10.1056/NEJM198711053171904. [DOI] [PubMed] [Google Scholar]
- zur Hausen H., Schulte-Holthausen H., Klein G., Henle W., Henle G., Clifford P., Santesson L. EBV DNA in biopsies of Burkitt tumours and anaplastic carcinomas of the nasopharynx. Nature. 1970 Dec 12;228(5276):1056–1058. doi: 10.1038/2281056a0. [DOI] [PubMed] [Google Scholar]