Skip to main content
SpringerLink
Log in

Prognostic significance of Ki-67 nuclear proliferative antigen, bcl-2 protein, and p53 expression in follicular and diffuse large B-cell lymphoma

  • Original Article
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

We analyzed 104 patients with non-Hodgkin’s lymphoma, follicular or diffuse large-B-cell-type lymphoma, in order to evaluate the correlation between clinical characteristics and immunohistochemical parameters. Immunostaining was performed by means of monoclonal antibodies against Ki-67, bcl-2, and p53 expression. Forty-nine of the patients showed follicular lymphoma. A high expression of bcl-2 was found in 93%, high expression of p53 in 57%, and low expression of Ki-67 in 96%. Follicular lymphoma grade III showed a p53 expression (p=0.07) slightly higher than follicular lymphoma grades I and II, not reaching statistical significance. Follicular lymphoma grades I and II tended to express lower Ki-67 and higher levels of bcl-2 expression than grade III (p=0.06). Fifty-five cases showed diffuse large-B-cell lymphoma. Among them, bcl-2 was absent in 39%, whereas p53 and Ki-67 expression were high in 38%. In the diffuse large-B-cell lymphomas, a high bcl-2 expression correlated with stages III and IV (p=0.03) and involvement of more than one extranodal area (p=0.03). High Ki-67 expression was also associated to extranodal involvement of more than one area (p=0.03). Overall survival of patients did not show statistically significant differences regarding Ki-67, bcl-2, and p53 tumoral expression. Prognostic factors for overall survival in the multivariate analysis were age (p=0.02) and LDH (p=0.003). Time to progression was worse among follicular lymphoma with high p53 expression than with mild/moderate p53 expression (p=0.009).

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

  1. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. (1993) A predictive model for aggressive non-Hodkin’s lymphoma. N. Engl. J. Med. 329:987–994.

    Article  Google Scholar 

  2. Swan, F., Velasquez, W.S., Tucker, S., et al. (1989). A new serologic lymphomas based on initial β2-microglobulin and lactate dehydrogenase levels. J. Clin. Oncol. 7:1518–1527.

    PubMed  Google Scholar 

  3. Hermine, O., et al. (1996). Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin’s lymphoma. Blood 87:265–272.

    PubMed  CAS  Google Scholar 

  4. Hill, M.E., MacLennan, K.A., Cunningham, D.C., et al. (1996). Prognostic significance of bcl-2 expression and bcl-2 major breakpoint region rearrangement in diffuse large cell non-Hodgkin’s lymphoma: a British National Lymphoma Investigation Study. Blood 88:1046–1051.

    PubMed  CAS  Google Scholar 

  5. Wilson W., Teruya-Feldstein J., Fest T., et al. (1997). Relationship of p53, bcl-2, and tumor proliferation to clinical drug resistance in non-Hodgkin’s lymphomas. Blood 89:601–609.

    PubMed  CAS  Google Scholar 

  6. Kramer, M.H.H, Hermans, J., Parker, J., et al. (1996). Clinical significance of bcl-2 and p53 protein expression in diffuse large B-cell lymphoma; a population based study. J. Clin. Oncol. 14:2131–2138.

    PubMed  CAS  Google Scholar 

  7. Cooper, K., and Haffajee, Z. (1997). Bcl-2 and p53 protein expression in follicular lymphoma. J. Pathol. 182:307–310.

    Article  PubMed  CAS  Google Scholar 

  8. Sander, C.A., Yano, T., Clark, H.M., et al. (1993). p53 mutation is associated with progression in follicular lymphomas. Blood 82:1994–2004.

    PubMed  CAS  Google Scholar 

  9. Adamson, D.J.A. Thompson, W.D., Dawson, A.A., Bennett, B., and Haites, E.N. (1995). p53 mutation and expression in lymphoma. Br. J. Cancer 72:150–154.

    PubMed  CAS  Google Scholar 

  10. Zoldan, M.A., Inghirami, G., Masuda, Y. and Vandekerckhove, R.B. (1996). Large cell variants of mantle cell lymphoma: cytologic characteristics and p53 anomalies may predict poor outcome. Br. J. Haematol. 93:475–486.

    Article  PubMed  CAS  Google Scholar 

  11. Greiner, T.C., Moynihan M.J., Chan W.C., et al. (1996). P53 mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis. Blood 87:4302–4310.

    PubMed  CAS  Google Scholar 

  12. Koduru, P.R.K., Raju, K., Vadmal. V., et al. (1997). Correlation between mutation in p53, p53 expression, cytogenetics, histologic type, and survival in patients with B-cell non-Hodgkin’s lymphoma. Blood 90:4078–4091.

    PubMed  CAS  Google Scholar 

  13. Hall, P.A., Richards, M.A., Gregory, W.M., et al. (1988). The prognostic value of Ki67 immunostaging in non-Hodgkin’s lymphoma. J. Pathol. 154:223–235.

    Article  PubMed  CAS  Google Scholar 

  14. Grogan, T.M., Lipprnan, S.M., Spier, C.M., et al. (1988). Independent prognostic significance of a nuclear proliferation antigen in diffuse large cell lymphomas as determined by the monoclonal antibody Ki67. Blood 71:1157–1160.

    PubMed  CAS  Google Scholar 

  15. Miller, T.P., Grogan, T.M., Dahlberg, S., et al. (1994). Prognostic significance of the Ki67 associated proliferate antigen in aggressive non-Hodgkin’s lymphomas: a prospective Southwest Oncology Group Trial. Blood 83:1460–1466.

    PubMed  CAS  Google Scholar 

  16. Grogan, T. (1998). Immunohisto-chemistry of lymphoma, in The Lymphomas (G. Canellos, T.A. Lister, and J.L. Sklar, eds.), pp. 151–183. W.B. Saunders Philadelphia.

    Google Scholar 

  17. Barnard, N.J., Hall, P.A., Lemoine, N.R. and Kadar, N. (1987). Proliferative index in breast carcinoma determined in situ by ki67 immunostaining and its relationship to clinical and pathological variables. J. Pathol. 152:287–295.

    Article  PubMed  CAS  Google Scholar 

  18. Kaplan, E.L. and Meier, P. (1958). Nonparametric estimation from incomplete observations. J. Am. Stat. Assoc. 53:457–481.

    Article  Google Scholar 

  19. Peto, R. and Peto, J. (1972). Asymptotically efficient rank invariant test procedures. J. Roy. Statist. Soc. A 35:185–206.

    Article  Google Scholar 

  20. Cox, D.R. (1972). Regressions model and life tables. J. Roy. Statist Soc. B 34:187–220.

    Google Scholar 

  21. Hiddemann, W., Longo, D.L., Coiffier, B., et al. (1996). Lymphoma classification: the gap between biology and clinical management is closing. Blood 88:4085–4089.

    PubMed  CAS  Google Scholar 

  22. Gascoyne, R. D. (1997). Pathologic prognostic factors in diffuse aggressive non-Hodgkin’s lymphoma. Hematol./Oncol. Clin. North Am. 11:847–862.

    Article  CAS  Google Scholar 

  23. Morente, M.M. (1998). Factores pronósticos en los linfomas no Hodgkinianos, in 5° Curso de Hematopatología, (T. Alvaro, R. Bosch, R. Font, S. Martínez, and M.T. Salvadó, eds.), pp. 131–152, Hosp Tortosa Verge de la Cinta, Tarragona, Spain.

    Google Scholar 

  24. Magrath, I. (1992). Molecular basis of lymphomagenesis. Cancer Res. 52(Suppl. 19):5529s-5540s.

    PubMed  CAS  Google Scholar 

  25. Reed, J.C. (1994). Bcl-2 and the regulation of programmed cell death. J. Cell Biol. 124:1–6.

    Article  PubMed  CAS  Google Scholar 

  26. Gaulard, P., d’Agay M.F., Peuelnnaur, M., et al. (1992). Expression of the bcl-2 gene product in follicular lymphoma. Ann. J. Pathol. 140:1089–1095.

    CAS  Google Scholar 

  27. Kondo, E., Yoshino, T., Yamadori, I., et al. (1994). Expression of bcl-2 protein and Fas antigen in Non-Hodgkin’s lymphomas. Ann. J. Pathol. 145:330–337.

    CAS  Google Scholar 

  28. Mrózek, K. and Bloomfield, C.D. (1998). Major cytogenetic findings in non-Hodgkin’s lymphoma, in The lymphomas, (G. Canellos, T.A. Lister, and J.L. Sklar, eds.), pp. 107–128, W.B. Saunders, Philadelphia.

    Google Scholar 

  29. Pezzella, F., Jones, M., Ralfkiaer, E., et al. (1992). Evaluation of bcl-2 protein expression and (14:18) translocation prognostic markers in follicular lymphoma. Br. J. Cancer 65:87–89.

    PubMed  CAS  Google Scholar 

  30. Yunis, J.J., Mayer, M.G., Arnesen, M.A., Aeppli, D.P., Oken, M.M. and Frizzera, G. (1989). Bcl-2 and other genomic alterations in the prognosis of large cell lymphoma. N. Engl. J. Med. 320:1047–1054.

    Article  PubMed  CAS  Google Scholar 

  31. Piris, M.A., Pezzella, F., Martinez-Montero, J.C., et al. (1994). P53 and bcl-2 expression in high grade B cell lymphomas: correlation with survival time. Br. J. Cancer 69:337–341.

    PubMed  CAS  Google Scholar 

  32. Levine, A.J., Momand, J. and Finlay, C.A. (1991). The p53 tumors suppressed gene. Nature 351:453.

    Article  PubMed  CAS  Google Scholar 

  33. Bauer, K.D., Merkel, D.E., Winter, J.N., et al. (1986) Prognostic implications of ploidy and proliferative activity in diffuse large cell lymphomas. Cancer Res. 46:3173.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain

    Hugo Alvarez-Argüelles & Lucio Díaz-Flores

  2. Department of Internal Medicine, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain

    Remedios Alemán

  3. Department of Medical Oncology, Hospital Universitario de Canarias, Ofra s/n, La Laguna, 38320, Santa Cruz de Tenerife, Spain

    Marta Llanos, Juana Oramas & Norberto Batista

Authors
  1. Marta Llanos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hugo Alvarez-Argüelles
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Remedios Alemán
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Juana Oramas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lucio Díaz-Flores
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Norberto Batista
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marta Llanos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Llanos, M., Alvarez-Argüelles, H., Alemán, R. et al. Prognostic significance of Ki-67 nuclear proliferative antigen, bcl-2 protein, and p53 expression in follicular and diffuse large B-cell lymphoma. Med Oncol 18, 15–22 (2001). https://doi.org/10.1385/MO:18:1:15

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/MO:18:1:15

Key Words

Search

Navigation