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Prognostic Significance of Survivin and Caspase-3 Immunohistochemical Expression in Patients with Diffuse Large B-cell Lymphoma Treated with Rituximab and CHOP

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Pathology & Oncology Research

Abstract

Survivin is an inhibitor of apoptosis whose expression may be associated with inferior outcome in patients with diffuse large B-cell lymphoma (DLBCL) treated without rituximab. Caspase-3 is the final caspase of the apoptotic cascade and its pattern of expression may also be related to patients’ outcome. In this study we investigated immunohistochemical expression of survivin and caspase-3 (CPP32) in 57 patients with DLBCL treated with rituximab and CHOP (R-CHOP). According to previously published criteria, we separately analyzed correlation of different types of survivin expression with patients’ outcome. Nuclear survivin was expressed in only 26% of cases, cytoplasmic survivin was expressed in 81% of cases while application of immunoreactivity scoring system yielded 58% of survivin positive cases. Caspase-3 was expressed in 77% of cases. There were no significant correlations between any type of survivin expression and response to treatment or survival of the patients. The expression of caspase-3 was also not associated with patients’ outcome. We conclude that survivin and caspase-3 have no significant prognostic significance in patients with DLBCL treated with R-CHOP.

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Abbreviations

NHL:

Non-Hodgkin’s lymphoma

DLBCL:

Diffuse large B-cell lymphoma

PS:

Performance status

ECOG:

Eastern Oncology Cooperative Group

IPI:

International prognostic index

LDH:

Lactate dehydrogenase

R-CHOP:

Rituximab, cyclophosphamide, doxorubicine, vincristin, prednisone

IAP:

Inhibitor of apoptosis

IRS:

Immunoreactivity scoring system

(u)CR:

(unconfirmed) complete remission

References

  1. Feugier P, Van Hoof A, Sebban C et al (2005) Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol 23:4117–4126

    Article  PubMed  CAS  Google Scholar 

  2. Pfreundschuh M, Trumper L, Osterborg A et al (2006) CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B cell lymphoma: a randomized controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol 7:379–391

    Article  PubMed  CAS  Google Scholar 

  3. Cvetkovic RS, Perry CM (2006) Rituximab—a review of its use in Non-Hodgkin’s lymphoma and chronic lymphocytic leukaemia. Drugs 66:791–820

    Article  PubMed  CAS  Google Scholar 

  4. Guha M, Altieri DC (2009) Survivin as a global target of intrinsic tumor suppression networks. Cell Cycle 8:2708–2710

    Article  PubMed  CAS  Google Scholar 

  5. Li F, Yang J, Ramnath N et al (2005) Nuclear or cytoplasmic expression of survivin: what is the significance? Int J Cancer 114:509–512

    Article  PubMed  CAS  Google Scholar 

  6. Watanuki-Miyauchi R, Kojima Y, Tsurumi H et al (2005) Expression of survivin and of antigen detected by a novel monoclonal antibody, T332, is associated with outcome of diffuse large B-cell lymphoma and its subtypes. Pathol Int 55:324–330

    Article  PubMed  CAS  Google Scholar 

  7. Karabatsou K, Pal P, Dodd S et al (2006) Expression of survivin, platelet-derived growth factor A (PDGF-A) and PDGF receptor alpha in primary central nervous system lymphoma. J Neurooncol 79:171–179

    Article  PubMed  CAS  Google Scholar 

  8. Lin L, Min Z, Ping Z (2007) Expression of PLK1 and survivin in diffuse large B-cell lymphoma. Leuk Lymphoma 48:2179–2183

    Article  Google Scholar 

  9. Mainou-Fowler T, Overman LM, Dignum H et al (2008) A new subtype-specific monoclonal antibody for IAP-survivin identifies high-risk patients with diffuse large B-cell lymphoma and improves the prognostic value of bcl-2. Int J Oncol 32:59–68

    PubMed  CAS  Google Scholar 

  10. Adida C, Haioun C, Gaulard P et al (2000) Prognostic significance of survivin expression in diffuse large B-cell lymphomas. Blood 96:1921–1925

    PubMed  CAS  Google Scholar 

  11. Aktaş S, Kargi A, Olgun N et al (2009) Prognostic significance of cell proliferation and apoptosis-regulating proteins in Epstein-Barr Virus positive and negative pediatric non-Hodgkin’s lymphoma. Pathol Oncol Res 15:345–350

    Article  PubMed  Google Scholar 

  12. Paydas S, Seydaoglu G, Ergin M et al (2009) Prognostic significance of angiogenic/lymphangiogenic, anti-apoptotic, inflammatory and viral factors in 88 cases with diffuse large B cell lymphoma and review of the literature. Leuk Res 33:1627–1635

    Article  PubMed  CAS  Google Scholar 

  13. Hans CP, Weisenburger DD, Greiner TC et al (2005) Expression of PKC-beta or cyclin D2 predicts for inferior survival in diffuse large B-cell lymphoma. Mod Pathol 18:1377–1384

    Article  PubMed  CAS  Google Scholar 

  14. Krajewski S, Gascoyne RD, Zapeta JM et al (1997) Immunolocalisation of the ICE/Ced 3-family protease, CPP32 (Caspase-3) in non-Hodgkin lymphomas, Chronic lymphocytic leukemias and reactive lymph nodes. Blood 89:3817–3825

    PubMed  CAS  Google Scholar 

  15. Donoghue S, Baden SH, Lauder I et al (1999) Immunohistochemical localization of caspase-3 correlates with clinical outcome in B-cell diffuse large cell lymphoma. Cancer Res 59:5386–5391

    PubMed  CAS  Google Scholar 

  16. ten Berge RL, Meijer CJ, Dukers DF et al (2002) Expression levels of apoptosis-related proteins predict clinical outcome in anaplastic large cell lymphoma. Blood 99:4540–4546

    Article  PubMed  Google Scholar 

  17. Muris JJ, Cillessen SA, Vos W et al (2005) Immunohistochemical profiling of caspase signalling pathways predicts clinical response to chemotherapy in primary nodal diffuse large B-cell lymphomas. Blood 105:2916–2923

    Article  PubMed  CAS  Google Scholar 

  18. Cheson BD, Horning SJ, Coiffier B et al (1999) Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. NCI Sponsored International Working group. J Clin Oncol 17:1244–1253

    PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

  20. Mounier N, Briere J, Gisselbrecht C et al (2003) Rituximab plus CHOP (R-CHOP) overcomes bcl-2-associated resistance to chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL). Blood 101:4279–4284

    Article  PubMed  CAS  Google Scholar 

  21. Ansell SM, Arendt BK, Grote DM et al (2004) Inhibition of survivin expression suppresses the growth of aggressive non-Hodgkin’s lymphoma. Leukemia 18:616–623

    Article  PubMed  CAS  Google Scholar 

  22. Tolcher AW, Mita A, Lewis LD et al (2008) Phase I and pharmacokinetic study of YM155, a small-molecule inhibitor of survivin. J Clin Oncol 26:5198–5203

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by grants from the Croatian Ministry of Science 108-1081872-1908 and 108-0000000-3426.

Conflict of Interest

Authors have no conflict of interest.

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Authors and Affiliations

  1. Division of Hematology and Department of Medicine, University Hospital Center Zagreb and School of Medicine University of Zagreb, Kispaticeva 12, 10 000, Zagreb, Croatia

    Zdravko Mitrović, Igor Aurer & Boris Labar

  2. Division of Hematology and Department of Medicine, University Hospital Center Zagreb, Zagreb, Croatia

    Sandra Bašić Kinda & Ivo Radman

  3. Department of Pathology, University Hospital Center Zagreb, Zagreb, Croatia

    Ivana Ilić & Snježana Dotlić

  4. Department of Medicine, University Hospital Dubrava, Av. Gojka Suska 6, 10 000, Zagreb, Croatia

    Radmila Ajduković

Authors
  1. Zdravko Mitrović
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  2. Ivana Ilić
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  3. Igor Aurer
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  4. Sandra Bašić Kinda
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  5. Ivo Radman
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  6. Snježana Dotlić
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  7. Radmila Ajduković
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  8. Boris Labar
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Corresponding author

Correspondence to Zdravko Mitrović.

Additional information

This article is in memory of our pathologist Marin Nola (1964–2008) who started this study.

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Mitrović, Z., Ilić, I., Aurer, I. et al. Prognostic Significance of Survivin and Caspase-3 Immunohistochemical Expression in Patients with Diffuse Large B-cell Lymphoma Treated with Rituximab and CHOP. Pathol. Oncol. Res. 17, 243–247 (2011). https://doi.org/10.1007/s12253-010-9304-4

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  • DOI: https://doi.org/10.1007/s12253-010-9304-4

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