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Prognostic significance of CD40 expression in malignant lymphoma developing in rheumatoid arthritis

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Abstract

Purpose: CD40, a member of tumor necrosis factor receptor superfamily, is expressed in synovial fluid B cells in rheumatoid arthritis (RA) and is postulated to contribute to RA progression. In this study, prognostic significance of CD40 expression was analyzed in B cell lymphoproliferative disorders (LPD) developing in RA. Method: CD40 expression was immunohistochemically examined in 35 cases of B-cell LPD developing in RA and in 32 of sporadic B-cell LPD as control. CD40 expression at mRNA level evaluated by quantitative reverse transcription-PCR and at protein level evaluated by immunohistochemistry correlated. Results: Frequency of diffuse large B-cell lymphoma (DLBCL) in RA- and sporadic-LPD was 71.4 and 59.3%, respectively. CD40 positive rate in RA-LPD (62.9%) was significantly higher than that in sporadic LPD (37.5%) (P=0.015). Interval between onset of RA and LPD development was shorter in CD40 positive cases than in negative cases (median 120 and 204 months, respectively) (P<0.07). Five-year survival rate in CD40 positive DLBCL cases (75%) was significantly better than that in negative cases (25%) (P<0.05). Conclusion: RA-LPD is characterized by the higher frequency of CD40 expression compared to sporadic LPD and CD40 positive cases which showed more favorable prognosis than those without CD40 expression.

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References

  • Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J Jr, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO, Staudt LM (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403:503–511

    Article  PubMed  CAS  Google Scholar 

  • Baecklund E, Ekbom A, Sparen P, Feltelius N, Klareskog L (1998) Disease activity and risk of lymphoma in patients with rheumatoid arthritis: nested case-control study. BMJ 317:180–181

    PubMed  CAS  Google Scholar 

  • Banchereau J, Bazan F, Blanchard D, Briere F, Galizzi JP, van Kooten C, Liu YJ, Rousset F, Saeland S (1994) The CD40 antigen and its ligand. Annu Rev Immunol 12:881–922

    Article  PubMed  CAS  Google Scholar 

  • Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-Lopez A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP (1999) Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphoma. J Clin Oncol 17:1244–1253

    PubMed  CAS  Google Scholar 

  • Cox DR (1972) Regression models and life tables. J Roy Stat Soc (B) 34:187–220

    Google Scholar 

  • French RR, Chan HT, Tutt AL, Glennie MJ (1999) CD40 antibody evokes a cytotoxic T-cell response that eradicates lymphoma and bypasses T-cell help. Nat Med 5:548–553

    Article  PubMed  CAS  Google Scholar 

  • Harney S, Wordsworth BP (2002) Genetic epidemiology of rheumatoid arthritis. Tissue Antigens 60:465–473

    Article  PubMed  CAS  Google Scholar 

  • Heid CA, Stevens J, Livak KJ, Williams PM (1996) Real time quantitative PCR. Genome Res 6:986–994

    Article  PubMed  CAS  Google Scholar 

  • Holland PM, Abramson RD, Watson R, Gelfand DH (1991) Detection of specific polymerase chain reaction product by utilizing the 5–3 exonuclease activity of Thermus aquaticus DNA polymerase. Proc Natl Acad Sci USA 88:7276–7280

    Article  PubMed  CAS  Google Scholar 

  • Hoshida Y, Tomita Y, Zhiming D, Yamauchi A, Nakatsuka S, Kurasono Y, Arima Y, Tsudo M, Shintaku M, Aozasa K (2004) Lymphoproliferative disorders in autoimmune diseases in Japan: analysis of clinicopathological features and Epstein-Barr virus infection. Int J Cancer 108:443–449

    Article  PubMed  CAS  Google Scholar 

  • Isler P, Vey E, Zhang JH, Dayer JM (1993) Cell surface glycoproteins expressed on activated human T cells induce production of interleukin-1 beta by monocytic cells: a possible role of CD69. Eur Cytokine Netw 4:15–23

    PubMed  CAS  Google Scholar 

  • Jaffe ES, Harris NL, Stein H, Vardinum JW eds (2001) Pathology and genetics, tumours of haematopoietic and lymphoid tissues, World Health Organization Classification of Tumours. IARC Press, Lyon

    Google Scholar 

  • Kaplan EL, Meier P (1958) Non-parametric estimation from incomplete observations. J Am Statist Assoc 53:457–481

    Article  Google Scholar 

  • Larsen CP, Elwood ET, Alexander DZ, Ritchie SC, Hendrix R, Tucker-Burden C, Cho HR, Aruffo A, Hollenbaugh D, Linsley PS, Winn KJ, Pearson TC (1996) Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways. Nature 381:434–438

    Article  PubMed  CAS  Google Scholar 

  • Li JM, Nichols MA, Chandrasekharan S, Xiong Y, Wang XF (1995) Contact-dependent stimulation of monocytic cells and neutrophils by stimulated human T-cell clones. Immunology 84:571–576

    PubMed  CAS  Google Scholar 

  • Linderoth J, Jerkeman M, Cavallin-Stahl E, Kvaloy S, Torlakovic E, Nordic Lymphoma Group Study (2003) Immunohistochemical expression of CD23 and CD40 may identify prognostically favorable subgroup of diffuse large B cell lymphoma: a Nordic lymphoma study. Clin Cancer Res 9:727–728

    Google Scholar 

  • Liu MF, Chao SC, Wang CR, Lei HY (2000) Expression of CD40 and CD40 ligand among cell population within rheumatoid synovial compartment. Autoimmunity 34:107–113

    Article  Google Scholar 

  • Szocinski JL, Khaled AR, Hixon J, Halverson D, Funakoshi S, Fanslow WC, Boyd A, Taub DD, Durum SK, Siegall CB, Longo DL, Murphy WJ (2002) Activation-induced cell death of aggressive histology lymphomas by CD40 stimulation: induction of bax. Blood 100:217–223

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto S, Tomita Y, Nakamori S, Hoshida Y, Nagano H, Dono K, Umeshita K, Sakon M, Monden M, Aozasa K (2003) Elevated expression of valosin-containing protein (p97) in hepatocellular carcinoma is correlated with increased incidence of tumor recurrence. J Clin Oncol 21:447–452

    Article  PubMed  CAS  Google Scholar 

  • Weiss LM, Chen YY, Liu XF, Shibata D (1991) Epstein-Barr virus and Hodgkin’s disease: a correlative in situ hybridization and polymerase chain reaction study. Am J Pathol 139:1259–1265

    PubMed  CAS  Google Scholar 

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Correspondence to Katsuyuki Aozasa.

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Supported in part by grants from the Ministry of Education, Science, Culture and Sports, Japan (15406013, 16390105, 16590277)

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Sasaki, T., Hoshida, Y., Xu, JX. et al. Prognostic significance of CD40 expression in malignant lymphoma developing in rheumatoid arthritis. J Cancer Res Clin Oncol 131, 797–802 (2005). https://doi.org/10.1007/s00432-005-0034-z

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