Skip to main content
Log in

The bcl-2/JH gene rearrangement is undetectable in Hodgkin's lymphomas: results from the German Hodgkin trial

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Ninety-one Hodgkin's lymphomas (HD), 52 non-Hodgkin lymphomas (NHL) and 33 specimens of non-neoplastic lymphatic tissues were investigated by polymerase chain reaction (PCR) for the presence of the bcl-2/JH gene rearrangement. The majority of the HD cases were drawn from the files of the German Hodgkin trial where diagnoses are established by a panel of four independent histopathologists. Using the very sensitive PCR method which detected 1 positive among 10000 negative cells, the bcl-2/JH gene rearrangement was found in 7/52 NHL and 3/16 tonsils with follicular hyperplasia, but in none of the 91 HD. The bcl-2 protein, however, was expressed by malignant cells of B and T cell lymphomas and by the giant tumour cells in 2/13 HD lymphocyte predominant, 11/28 HD nodular sclerosing I, 14/17 HD nodular sclerosing II, 10/27 HD mixed cellularity and 3/3 HD lymphocyte depleted. The bcl-2/JH rearrangement is thus independent of protein over-expression, the latter being found in all types of lymphomas. Our results do not confirm the findings of others who have detected the bcl-2/JH rearrangement in HD. These discrepancies may be explained by differences in choice of material, the gene rearrangement actually occuring in bystander cells but not in Reed-Sternberg or Hodgkin cells, or by contamination.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Algara P, Martinez P, Sanchez L, Villuendas R, Orradre JL, Oliva H, Piris MA (1991) Lymphocyte predominance Hodgkin's disease (nodular paragranuloma)-a bcl-2 negative germinal centre lymphoma. Histopathology 19:69–75

    Google Scholar 

  2. Aster JC, Kobayashi Y, Shiota M, Mori S, Sklar J (1992) Detection of the t(14;18) at similar frequencies in hyperplastic lymphoid tissues from American and Japanese patients. Am J Pathol 141:291–299

    Google Scholar 

  3. Athan E, Chadburn A, Knowles DM (1992) The bcl-2 gene translocation is undetectable in Hodgkin's disease by Southern blot hybridization and polymerase chain reaction. Am J Pathol 141:193–201

    Google Scholar 

  4. Chleq-Deschamps CM, LeBrun DP, Huie P, Besnier DP, Warnke RA, Sibley RK, Cleary ML (1993) Topographical dissociation of bcl-2 messenger RNA and protein expression in human lymphoid tissues. Blood 81:293–298

    Google Scholar 

  5. Cleary ML, Galili N, Sklar J (1986) Detection of a second t(14;18) breakpoint cluster region in follicular lymphomas. J Exp Med 164:315–320

    Google Scholar 

  6. Cordell JR, Falini B, Erber WN, Ghosh AK, Abdulaziz Z, MacDonald S, Pulford KA, Stein H, Mason DY (1984) Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 32:219–229

    CAS  PubMed  Google Scholar 

  7. Creszenzi M, Seto M, Herzig GP, Weiss PD, Griffith RC, Korsmeyer SJ (1988) Thermostable DNA polymerase chain amplification of t(14;18) chromosome breakpoints and detection of minimal residual disease. Proc Natl Acad Sci USA 85:4869–4873

    Google Scholar 

  8. Georgii A (1993) Histopathologie und Zellbiologie der Hodgkin-Lymphome. Der Internist 34:97–105

    Google Scholar 

  9. Georgii A, Fischer R, Hübner K, Schwarze EW, Bernhards J (1993) Classification of Hodgkin's disease biopsies by a panel of 4 histopathologists. Report of 1140 patients from the German National Trial. Leukemia & Lymphoma 9:365–370

    Google Scholar 

  10. Gonzalez CL, Medeiros LJ, Jaffe ES (1991) Composite lymphoma. A clinicopathologic analysis of nine patients with Hodgkin's disease and B-cell non-Hodgkin's lymphoma. Am J Clin Pathol 96:81–89

    Google Scholar 

  11. Gupta RK, Whelan JS, Andrew Lister T, Young BD, Bodmer JG (1992) Direct sequence analysis of the t(14;18) chromosomal translocation in Hodgkin's disease. Blood 79:2084–2088

    Google Scholar 

  12. Gupta RK, Lister TA, Bodmer JG (1994) The t(14;18) chromosomal translocation and bcl-2 protein expression in Hodgkin's disease. Leukemia 8:1337–1341

    Google Scholar 

  13. Kluin-Nelemans HC, Limpens J, Meerabux J, Beverstock GC, Jansen JH, deJong D, Kluin PM (1991) A new non-Hodgkin's B-cell line (DoHH2) with a chromosomal translocation t(14;18) (q32;q21). Leukemia 5:221–224

    Google Scholar 

  14. Kneba M, Eick S, Herbst H, Willigeroth S, Pott C, Bolz I, Bergholz M, Neumann C, Stein H, Krieger G (1991) Frequency and structure of t(14;18) major breakpoint regions in non-Hodgkin's lymphomas typed according to the Kiel classification: analysis by direct DNA sequencing. Cancer Res 51:3243–3250

    Google Scholar 

  15. Kondo E, Nakamura S, Onoue H, Matsuo Y, Yoshino T, Aoki H, Hayashi K, Takahashi K, Minowada J, Nomura S, Akagi T (1992) Detection of bcl-2 protein and bcl-2 messenger RNA in normal and neoplastic lymphoid tissues by immunohistochemistry and in situ hybridization. Blood 80:2044–2051

    Google Scholar 

  16. Korsmeyer SJ (1992) Bcl-2 initiates a new category of oncogenes: regulators of cell death. Blood 80:879–886

    Google Scholar 

  17. Limpens J, deJong D, vanKrieken JHJM, Price CGA, Young BD, vanOmmen GJB, Kluin PM (1991) Bcl-2/JH rearrangements in benign lymphoid tissues with follicular hyperplasia. Oncogene 6:2271–2276

    Google Scholar 

  18. Limpens J, Beelen M, Stad R, Havwerkort M, van Krieken JHJM, vanOmmen GJB, Kluin PM (1993) Detection of the t(14;18) translocation in frozen and formalin-fixed tissue. DMP 2:99–107

    Google Scholar 

  19. Lorenzen J, Hansmann ML, Pezzella F, Hesse C, Kneba M, Gatter KC, Fischer R (1992) Expression of the bcl-2 oncogene product and chromosomal translocation t(14;18) in Hodgkin's disease. Hum Pathol 23:1205–1209

    Google Scholar 

  20. Louie DC, Kant JA, Brooks JJ, Reid JC (1991) Absence of t(14;18) major and minor breakpoints and of bcl-2 protein overproduction in Reed-Sternberg cells of Hodgkin's disease. Am J Pathol 139:1231–1237

    Google Scholar 

  21. MacLennan MA, Bennett MH, Tu A, Vaughan Hudson B, Easterling J, Vaughan Hudson G, Jelliffe AM (1989) Relationship of histopathologic features to survival and relapse in nodular sclerosing Hodgkin's disease. Cancer 64:1686–1693

    Google Scholar 

  22. Nolte M, Werner M, Spann W, Schnabel B, von Wasielewski R, Wilkens L, Georgii A (1993) Nachweis des bcl-2/JH Genrearrangements in Non-Hodgkin Lymphomen und chronischer Tonsillitis, nicht aber in Hodgkin-Lymphomen. Pathologe 14:302–306

    Google Scholar 

  23. Pezzella F, Tse AGD, Cordell JL, Pulford KAF, Gatter KC, Mason DY (1990a) Expression of the bcl-2 oncogene protein is not specific for the 14;18 chromosomal translocation. Am J Pathol 137:225–232

    Google Scholar 

  24. Pezzella F, et al. (1990b) Bcl-2 protein expression in follicular lymphomas in absence of 14;18 translocation. Lancet 336:1510–1511

    Google Scholar 

  25. Poppema S, Kaleta J, Hepperle B (1992) Chromosomal abnormalities in patients with Hodgkin's disease: evidence for frequent involvement of the 14q chromosomal region but infrequent bcl-2 gene rearrangement in Reed-Sternberg cells. J Natl Cancer Inst 84:1789–1793

    Google Scholar 

  26. Reid AH, Cunningham RE, Frizzera G, O'Leary T (1993) Bcl-2 rearrangement in Hodgkin's disease. Am J Pathol 142:395–402

    Google Scholar 

  27. Said JW, Sassoon AF, Shintaku IP (1990) Polymerase chain reaction for bcl-2 in diagnostic lymph node biopsies. Modern Pathol 3:659–663

    Google Scholar 

  28. Said JW, Sassoon AF, Shintaku IP, Kurtin PJ, Pinkus GS (1991) Absence of bcl-2 major breakpoint region and JH gene rearrangement in lymphocyte predominance Hodgkin's disease. Am J Pathol 138:261–264

    Google Scholar 

  29. Said JW, Pinkus GS, Lones MA, Preston M, Shintaku IP (1993) Expression of bcl-2 oncogene protein in malignant lymphomas, including Hodgkin's disease and non-Hodgkin's lymphomas of T-cell phenotype. Appl Immunohistochem 1:108–114

    Google Scholar 

  30. Sambrook J, Fritsch EF, Maniatis T (1993) Molecular cloning. A laboratory manual, 2, vol 1–3, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, USA

    Google Scholar 

  31. Segal GH, Scott M, Jorgensen T, Braylan RC (1994) Primers frequently used for detecting the t(14;18) major breakpoint also amplify Epstein-Barr viral DNA. Diagn Mol Pathol 3:15–21

    Article  CAS  PubMed  Google Scholar 

  32. Shibata D, Hu E, Weiss LM, Brynes RK, Nathwani BN (1990) Detection of specific t(14;18) chromosomal translocations in fixed tissues. Hum Pathol 21:199–203

    Google Scholar 

  33. Southern EM (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 98:503–517

    CAS  PubMed  Google Scholar 

  34. Stetler-Stevenson M, Crush-Stanton S, Cossman J (1990) Involvement of the bcl-2 gene in Hodgkin's disease. J Natl Cancer Inst 82:855–858

    Google Scholar 

  35. Stetler-Stevenson M (1992) The t(14;18) translocation in Hodgkin's disease (editorial). J Natl Cancer Inst 84:1170–1171

    Google Scholar 

  36. Tanaka S, Kant J, Reed JC (1991) G to A polymorphism in the second exon of the bcl-2 gene. Nucl Acids Res 19:1964

    Google Scholar 

  37. Tsujimoto Y, Yunis JJ, Nowell PC, Croce C (1984) Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science 226:1097–1099

    Google Scholar 

  38. Vaux DL, Cory S, Adams JM (1988) Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 335:440

    Google Scholar 

  39. Yunis JJ, Frizzera G, Oken MM, McKenna J, Theologides A, Arnesen M (1987) Multiple recurrent genomic defects in follicular lymphoma. N Engl J Med 317:1185–1189

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nolte, M., Werner, M., von Wasielewski, R. et al. The bcl-2/JH gene rearrangement is undetectable in Hodgkin's lymphomas: results from the German Hodgkin trial. Vichows Archiv A Pathol Anat 426, 37–41 (1995). https://doi.org/10.1007/BF00194696

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00194696

Key words

Navigation