Advertisement

International Journal of Hematology

, Volume 85, Issue 1, pp 41–48 | Cite as

Clinicopathologic Significance of Loss of CD19 Expression in Diffuse Large B-Cell Lymphoma

  • Miho Kimura
  • Motoko Yamaguchi
  • Shigeo Nakamura
  • Hiroshi Imai
  • Satoshi Ueno
  • Shoko Ogawa
  • Kana Miyazaki
  • Kouji Oka
  • Toshiyuki Ohno
  • Kenkichi Kita
  • Tohru Kobayashi
  • Hiroshi Shiku
Article

Abstract

To clarify the clinicopathologic significance of a loss of CD19 expression in diffuse large B-cell lymphoma (DLBCL), we evaluated CD19 expression immunohistochemically in frozen sections from 227 patients who had received diagnoses of DLBCL according to the World Health Organization classification between 1987 and 2002. Histopathologic features of patients with CD19- DLBCL were reviewed, and their clinical features, immunophenotypes, and prognoses were compared retrospectively with respect to CD19 expression. CD19 expression was positive in 205 patients (90%). The 22 patients with CD19- DLBCL had a median age of 63 years, and the male-female ratio was 11:11. Compared with patients with CD19+ DLBCL, those with CD19- DLBCL more frequently showed elevated lactate dehydrogenase (LDH) levels (73%, P = .011). Morphologically, 15 (79%) of the 19 CD19- DLBCL patients examined showed plasmablastic/plasmacytoid differentiation. Patients with CD19- DLBCL expressed BCL2 protein less frequently than CD19+ DLBCL (P = .042). Especially noteworthy is that half of the patients with CD19- DLBCL died within 2 years after diagnosis. The CD19- DLBCL group showed a survival curve significantly inferior to that for the CD19+ group (P = .034, generalized Wilcoxon test). Our findings demonstrate that loss of CD19 expression in DLBCL is associated with elevated serum LDH levels and a poor prognosis, especially during the early follow-up period.

Key words

Non-Hodgkin’s lymphoma Cell surface antigens Immunocytochemistry Immunophenotype Prognostic factors 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Tedder TF, Zhou LJ, Engel P. The CD19/CD21 signal transduction complex of B lymphocytes. Immunol Today. 1994;15:437–442.CrossRefPubMedGoogle Scholar
  2. 2.
    Harada H, Kawano MM, Huang N, et al. Phenotypic difference of normal plasma cells from mature myeloma cells. Blood. 1993;81:2658–2663.PubMedGoogle Scholar
  3. 3.
    Nadler LM, Anderson KC, Marti G, et al. B4, a human B lymphocyte-associated antigen expressed on normal, mitogen-activated, and malignant B lymphocytes. J Immunol. 1983;131:244–250.PubMedGoogle Scholar
  4. 4.
    Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. World Health Organization Classification of Tumours. Pathology & Genetics: Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001.Google Scholar
  5. 5.
    Konoplev S, Medeiros LJ, Bueso-Ramos CE, Jorgensen JL, Lin P. Immunophenotypic profile of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. Am J Clin Pathol. 2005;124:414–420.CrossRefPubMedGoogle Scholar
  6. 6.
    Harris NL, Jaffe ES, Stein H, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994;84:1361–1392.Google Scholar
  7. 7.
    Gatter KC, Warnke RA. Diffuse large B-cell lymphoma. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. World Health Organization Classification of Tumours. Pathology & Genetics:Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001:171–174.Google Scholar
  8. 8.
    Harada S, Suzuki R, Uehira K, et al. Molecular and immunological dissection of diffuse large B cell lymphoma: CD5+, and CD5- with CD10+ groups may constitute clinically relevant subtypes. Leukemia. 1999;13:1441–1447.CrossRefPubMedGoogle Scholar
  9. 9.
    Yamaguchi M, Seto M, Okamoto M, et al. De novo CD5+ diffuse large B-cell lymphoma: a clinicopathologic study of 109 patients. Blood. 2002;99:815–821.CrossRefPubMedGoogle Scholar
  10. 10.
    Linderoth J, Jerkeman M, Cavallin-Ståhl E, Kvaløy S,Torlakovic E. Immunohistochemical expression of CD23 and CD40 may identify prognostically favorable subgroups of diffuse large B-cell lym- phoma: a Nordic Lymphoma Group Study. Clin Cancer Res. 2003;9:722–728.PubMedGoogle Scholar
  11. 11.
    Ohshima K, Kawasaki C, Muta H, et al. CD10 and Bcl10 expression in diffuse large B-cell lymphoma: CD10 is a marker of improved prognosis. Histopathology. 2001;39:156–162.CrossRefPubMedGoogle Scholar
  12. 12.
    Hans CP, Weisenburger DD, Greiner TC, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103:275–282.CrossRefPubMedGoogle Scholar
  13. 13.
    Ogawa S, Yamaguchi M, Oka K, et al. CD21S antigen expression in tumour cells of diffuse large B-cell lymphomas is an independent prognostic factor indicating better overall survival. Br J Haematol. 2004;125:180–186.CrossRefPubMedGoogle Scholar
  14. 14.
    Delecluse HJ, Anagnostopoulos I, Dallenbach F, et al. Plasma-blastic lymphomas of the oral cavity: a new entity associated with the human immunodeficiency virus infection. Blood. 1997;89:1413- 1420.PubMedGoogle Scholar
  15. 15.
    Freedman AS, Boyd AW, Anderson KC, et al. Immunologic heterogeneity of diffuse large cell lymphoma. Blood. 1985;65:630–637.PubMedGoogle Scholar
  16. 16.
    Picker LJ, Weiss LM, Medeiros LJ, Wood GS, Warnke RA. Immunophenotypic criteria for the diagnosis of non-Hodgkin’s lymphoma. Am J Pathol. 1987;128:181–201.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Schuurman HJ, van Baarlen J, Huppes W, Lam BW, Verdonck LF, van Unnik JAM. Immunophenotyping of non-Hodgkin’s lym-phoma: lack of correlation between immunophenotype and cell morphology. Am J Pathol. 1987;129:140–151.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Meeker TC, Miller RA, Link MP, Bindl J, Warnke R, Levy R. A unique human B lymphocyte antigen defined by a monoclonal antibody. Hybridoma. 1984;3:305–320.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Yang W, Agrawal N, Patel J, et al. Diminished expression of CD19 in B-cell lymphomas. Cytometry B Clin Cytom. 2005;63:28–35.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Masir N, Marafioti T, Jones M, et al. Loss of CD19 expression in B-cell neoplasms. Histopathology. 2006;48:239–246.CrossRefPubMedGoogle Scholar
  21. 21.
    Oka K, Ohno T, Kita K, et al. PRAD1 gene over-expression in mantle-cell lymphoma but not in other low-grade B-cell lym-phomas, including extranodal lymphoma. Br J Haematol. 1994;86:786–791.CrossRefPubMedGoogle Scholar
  22. 22.
    Hermine O, Haioun C, Lepage E, et al. Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin’s lymphoma: Groupe d’Etude des Lymphomes de l’Adulte (GELA). Blood. 1996;87:265–272.PubMedGoogle Scholar
  23. 23.
    The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin’s lym-phoma. N Engl J Med. 1993;329:987–994.CrossRefGoogle Scholar
  24. 24.
    Lennert K, Feller AC. Histopathology of Non-Hodgkin’s Lym- phomas. Based on the Updated Kiel Classification. 2nd ed. Berlin, Germany: Springer-Verlag; 1992.CrossRefGoogle Scholar
  25. 25.
    Gaidano G, Cerri M, Capello D, et al. Molecular histogenesis of plasmablastic lymphoma of the oral cavity. Br J Haematol. 2002;119:622–628.CrossRefPubMedGoogle Scholar
  26. 26.
    Chetty R, Hlatswayo N, Muc R, Sabaratnam R, Gatter K. Plasmablastic lymphoma in HIV+ patients: an expanding spectrum. Histopathology. 2003;42:605–609.CrossRefPubMedGoogle Scholar
  27. 27.
    Teruya-Feldstein J, Chiao E, Filippa DA, et al. CD20-negative large-cell lymphoma with plasmablastic features: a clinically heterogeneous spectrum in both HIV-positive and -negative patients. Ann Oncol. 2004; 15:1673–1679.CrossRefPubMedGoogle Scholar
  28. 28.
    Colomo L, Loong F, Rives S, et al. Diffuse large B-cell lymphomas with plasmablastic differentiation represent a heterogeneous group of disease entities. Am J Surg Pathol. 2004;28:736–747.CrossRefPubMedGoogle Scholar
  29. 29.
    Dong HY, Scadden DT, de Leval L, Tang Z, Isaacson PG, Harris NL. Plasmablastic lymphoma in HIV-positive patients: an aggressive Epstein-Barr virus-associated extramedullary plasmacytic neoplasm. Am J Surg Pathol. 2005;29:1633–1641.CrossRefPubMedGoogle Scholar
  30. 30.
    Simonitsch-Klupp I, Hauser I, Ott G, et al. Diffuse large B-cell lym- phomas with plasmablastic/plasmacytoid features are associated with TP53 deletions and poor clinical outcome. Leukemia. 2004;18:146–155.CrossRefPubMedGoogle Scholar
  31. 31.
    Kimura M, Yamaguchi M, Ueno S, et al. CD19-negative diffuse large B-cell lymphoma shows high serum LDH level and poor prognosis [abstract]. Blood. 2005;106:546a.CrossRefGoogle Scholar
  32. 32.
    The Non-Hodgkin’s Lymphoma Classification Project. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. Blood. 1997;89:3909- 3918.Google Scholar
  33. 33.
    Mahmoud MS, Fujii R, Ishikawa H, Kawano MM. Enforced CD19 expression leads to growth inhibition and reduced tumorigenicity. Blood. 1999;94:3551–3558.PubMedGoogle Scholar
  34. 34.
    Mounier N, Briere J, Gisselbrecht C, et al. Rituximab plus CHOP (R-CHOP) overcomes bcl-2-associated resistance to chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL). Blood. 2003;101:4279–4284.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2007

Authors and Affiliations

  • Miho Kimura
    • 1
  • Motoko Yamaguchi
    • 1
  • Shigeo Nakamura
    • 3
  • Hiroshi Imai
    • 2
  • Satoshi Ueno
    • 1
  • Shoko Ogawa
    • 1
  • Kana Miyazaki
    • 1
  • Kouji Oka
    • 4
  • Toshiyuki Ohno
    • 5
  • Kenkichi Kita
    • 6
  • Tohru Kobayashi
    • 1
  • Hiroshi Shiku
    • 1
  1. 1.Department of HematologyMie University Graduate School of MedicineJapan
  2. 2.Pathologic OncologyMie University Graduate School of MedicineTsuJapan
  3. 3.Department of Pathology and Clinical LaboratoriesNagoya University HospitalNagoyaJapan
  4. 4.Department of Internal MedicineSuzuka Kaisei General HospitalSuzukaJapan
  5. 5.Ohno ClinicOhuchiyamaJapan
  6. 6.Tokura HospitalUjiJapan

Personalised recommendations