Skip to main content

Advertisement

SpringerLink
Log in

Apoptosis, proliferative activity and Bcl-2 expression in Epstein-Barr-virus-positive non-Hodgkin's lymphomas

  • Original Paper
  • Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

In order to clarify the effects of Epstein-Barr virus (EBV) infection on apoptosis and proliferative activity of non-Hodgkin's lymphoma, 135 Japanese lymphoma cases were investigated for the presence of viral RNA and its correlation withbcl-2 protein (Bcl-2) expression. In addition, the role of EBV in lymphomagenesis was also studied in terms of EBV genotyping and specific deletion in the gene for the latent membrane protein 1(LMP-1). EBER-1 RNA in situ hybridization revealed EBV in 18 cases (13.3%), comprising 12 of 44 T cell (27.3%) and 6 of 91 B cell (6.6%) lymphomas. Type A EBV was found in all 18 cases (100%), and 17 of the 17 (100%) evaluable cases showed a 30-bp deletion within the 3′ end ofLMP-1. Comparison of apoptotic indices (AI), assessed by DNA nick-end labelling, and proliferative activity, estimated in terms of Ki-67 labelling and mitotic indices (KI and MI), demonstrated an overall correlation among AI, KI and MI increases in association with Bcl-2 negativity, indicating a close relation between apoptosis and proliferation. EBV-positive cases showed significantly elevated AI values, independent of Bcl-2 positivity, with no change in KI and MI. These results indicate that EBV in Japanese non-Hodgkin's lymphomas is exclusively of type A with a specific deletion inLMP-1 and that it tends to be present in T cell lymphomas. Moreover, EBV up-regulates apoptosis without any relation to Bcl-2 expression and exerts only minor effects on proliferation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Chen ML, Tsai CN, Liang CL, Shu CN, Hang CR, Sulitzeann D, Linst ST, Chang YS (1992) Cloning and characterization of the latent membrane protein (LMP) of specific Epstein-Barr virus variant derived from the nasopharyngeal carcinoma in Taiwanese population. Oncogene 7:2131–2140

    Google Scholar 

  • Chen WG, Chen YY, Bacchi MM, Alvarenga M, Weiss LM (1996) Genotyping of Epstein-Barr virus in Brazilian Burkitt's lymphoma and reactive lymphoid tissue: type A with a high prevalance of deletions within the latent membrane protein gene. Am J Pathol 148:17–23

    Google Scholar 

  • Columbano A, Ledda-Columbano GM, Rao PM, Rajalakshmi S, Sarma DSR (1984) Occurence of cell death (apoptosis) in preneoplastic and neoplastic cells: a sequential study. Am J Pathol 116:441–446

    Google Scholar 

  • Fingeroth JD, Weiss JJ, Tedder TF, Strominger JL, Biro PA, Fearon DT (1984) Epstein-Barr virus receptor of human B lymphocytes is the C3d receptor CR2. Proc Natl Acad Sci USA 81:4510–4514

    Google Scholar 

  • Frank D, Cesarman E, Liu YF, Michler RE, Knowles DM (1995) Post-transplantation lymphoproliferative disorders frequently contain type A and not type B Epstein-Barr virus. Blood 85:1396–1403

    Google Scholar 

  • Gregory CD, Dive C, Henderson S, Smith C, Williams GT, Gordon J, et al (1991) Activation of Epstein-Barr virus latent genes protects human B cells from death by apoptosis. Nature 349:612–614

    Google Scholar 

  • Hamilton-Dutoit SJ, Pallesen G, Franzmann MB, Karkov J, Black F, Skinhoj P, Pedersen C (1991) AIDS-related lymphoma. Histopathology, immunophenotype, and association with Epstein-Barr virus as demonstrated by in situ nucleic acid hybridization. Am J Pathol 138:149–163

    Google Scholar 

  • Hamilton-Dutoit SJ, Pallesen G (1992) A survey of Epstein-Barr gene expression in sporadic non-Hodgkin's lymphomas. Detection of Epstein-Barr virus in a subset of peripheral T-cell lymphomas. Am J Pathol 335:128–130

    Google Scholar 

  • Henderson S, Rowe M, Gregory C, Croom-Carter D, Wang F, Longnecker R, Kieff E, Rickenson A (1991) Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell 65:1107–1115

    Google Scholar 

  • Hockenbery DM, Zutter M, Hickey W, Nahm M, Korsmeyer SJ (1991) BCL-2 protein is topographically restricted in tissues by apoptotic cell death. Proc Natl Acad Sci USA 88:6961–6965

    Google Scholar 

  • Hu LF, Chen F, Cheng X, Ernberg I, Cao SL, Christensson B, Klein G, Weinberg G (1993) Clonability and tumorigenicity of human epithelial cells expressing the EBV encoded membrane proteinLMP-1. Oncogene 8:1573–1583

    Google Scholar 

  • Kanavaros P, Briere J, Lescs MC, Gaulard P (1996) Epstein-Barr virus in non-Hodgkin's lymphomas of the upper respiratory tract: association with sinonasal localisation and expression of NK and/or T cell antigens by tumour cells. J Pathol 178:297–302

    Google Scholar 

  • Kerr JFR, Winterford CM, Harmon BV (1994) Apoptosis: its significance in cancer and cancer therapy. Cancer 73:2013–2026

    Google Scholar 

  • Kieff E, Liebowitz D (1990) Epstein-Barr virus and its replication. In: Fields BN, Knipe DM (eds) Virology. Raven, New York, pp. 1889–1920

    Google Scholar 

  • Lee ES, Locker J, Nalesnik M, Reyes J, Jaffe R, Alashari M, Nour B, Tzakis A, Dickman PS (1995) The association of Epstein-Barr virus with smooth-muscle tumours occurring after organ transplantation. N Engl J Med 332:19–25

    Google Scholar 

  • Leonichi L, Del Vecchio MT, Barbini P, Galieni P, Pileri S, Sabattini E, Gherlinzoni F, Tosi P, Kraft R, Cottier H (1993) Correlation between apoptotic and proliferative indices in malignant non-Hodgkin's lymphomas. Am J Pathol 142:755–763

    Google Scholar 

  • Nathwani BN, Brynes RK, Lincolin T, Hansmann ML (1992) Classification of non-Hodgkin's lymphomas. In: Knowles DM (ed) Neoplastic haematology. Williams & Wilkins, Baltimore, Md, pp. 555–601

    Google Scholar 

  • Purtilo DT, Strobach RS, Okano M, Davis JR (1992) Biology of disease: Epstein-Barr virus-associated lymphoproliferative disorders. Lab Invest 67:5–23

    Google Scholar 

  • Raff MC (1992) Social control of cell survival and cell death. Nature 356:357–400

    Google Scholar 

  • Rickinson AB, Young LS, Rowe M (1987) Influence of the Epstein-Barr virus nuclear antigenEBNA-2 on the growth phenotype of virus-transformed B cells. J Virol 61:1310–1317

    Google Scholar 

  • Rowe M, Rowe DT, Gregory CD, Young LS, Farrel PJ, Rupani H, Rickenson AB (1987) Differences in B cell growth phenotype reflect novel patterns of Epstein-Barr virus latent gene expression in Burkitt's lymphoma cells. EMBO J 6:2743–2751

    Google Scholar 

  • Sculley TB, Apollini A, Hurren L, Moss DE, Cooper D (1990) Coinfection with A- and B-type Epstein-Barr virus in human immunodeficiency virus-positive subjects. J Infect Dis 162:643–48

    Google Scholar 

  • Shi Y, Glynn JM, Guilbert LJ, Cotter TG, Bissonnette RP, Green DR (1992) Role forc-myc in activation-induced apoptotic cell death in T cell hybridomas. Science 257:212–214

    Google Scholar 

  • Purtilo DT, Strobach RS, Okano M, Davis JR (1992) Biology of disease: Epstein-Barr virus-associated lymphoproliferative disorders. Lab Invest 67:5–23

    Google Scholar 

  • Sample J, Young L, Martin B, Chatman T, Kieff E, Rickenson AB (1990) Epstein-Barr virus type 1, and 2 differ in theEBNA-3A, EBNA-3B andEBNA-3C genes. J Virol 64:4084–4092

    Google Scholar 

  • Takano Y, Kato Y (1995) Epstein-Barr virus association with early cancers found together with gastric medullary carcinomas demonstrating lymphoid infiltration. J Pathol 175:39–44

    Google Scholar 

  • Takano Y, Colanzi RP, Shiga J (1994) High incidence of Epstein-Barr virus associated non-Hodgkin's lymphomas in the Bolivian mountains. Pathol Int 44:237–240

    Google Scholar 

  • Takano Y, Saegusa M, Ikenaga M, Mitomi H, Okayasu I (1996) Apoptosis of colon cancer: comparison with Ki-67 proliferative activity and expression of p53. J Cancer Res Clin Oncol 122:166–170

    Google Scholar 

  • Takano Y, Saegusa M, Ikenaga M, Okayasu I (1997) Apoptosis and proliferative activity of non-Hodgkin's lymphomas: comparison with expression of bcl-2, p53 and c-myc proteins. Pathol Int 47:90–94

    Google Scholar 

  • Theodorou I, Bigorgne C, Delfau MH, Lahet C, Cochet G, Vidard M, Raphael M, Gaulard P, Farcet JP (1996) Vj rearrangement of the TCRγ locus in peripheral T-cell lymphomas: analysis by polymerase chain reaction and denaturing gradient gel electrophoresis. J Pathol 178:303–310

    Google Scholar 

  • Tsujimoto Y, Ikegami N, Crose CM (1987) Characterisation of the protein product ofbcl-2, the gene involved in human follicular lymphoma. Oncogene 2:3–7

    Google Scholar 

  • Yonishi-Rouach E, Resnitzky D, Lotem J, Kimchi A, Orem M (1991) Wild-type p53 induces apoptosis of myeloid leukemia cells that is inhibited by interleukin-6. Nature 352:345–347

    Google Scholar 

  • Young LS, Rowe M (1992) Epstein-Barr virus, lymphomas and Hodgkin's disease. Semin Cancer Biol 3:273–284

    Google Scholar 

  • Young LS, Yao QY, Roponey CM, Sculley TB, Moss DJ, Rupani H, Laux G, Mornkamm GW (1987) New type B isolate of Epstein-Barr virus from Burkitt's lymphoma and normal individuals in an endemic area. J Gen Viol 68:2853–2862

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, 228, Sagamihara, Kanagawa, Japan

    Yasuo Takano, Makoto Saegusa, Tetsuo Mikami & Isao Okayasu

  2. Department of Urology, Yokohama Municipal University School of Medicine, 3-9 Fuku-ura, Kanazawa, 236, Yokohama, Kanagawa, Japan

    Mitsunobu Masuda

Authors
  1. Yasuo Takano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Makoto Saegusa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mitsunobu Masuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tetsuo Mikami
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Isao Okayasu
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Takano, Y., Saegusa, M., Masuda, M. et al. Apoptosis, proliferative activity and Bcl-2 expression in Epstein-Barr-virus-positive non-Hodgkin's lymphomas. J Cancer Res Clin Oncol 123, 395–401 (1997). https://doi.org/10.1007/BF01240123

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01240123

Key words

Search

Navigation