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Immunohistological profiling by B-cell differentiation status of primary central nervous system lymphoma treated by high-dose methotrexate chemotherapy

  • Clinical Study - Patient Study
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Abstract

Primary central nervous system lymphoma (PCNSL) remains a devastating disease with poor prognosis, despite the improvement offered by methotrexate (MTX)-based chemotherapy. Several studies have attempted to identify biomarkers predictive of prognosis, which are expected to be both clinically useful and biologically important for understanding PCNSL. The present study attempts to classify human immunodeficiency virus (HIV)-unrelated PCNSL patients treated with radiation combined with rapid high-dose MTX chemotherapy according to B-cell differentiation status, and retrospectively examines the prognostic impact. Initial response to MTX was a strong predictor of favorable prognosis in terms of both progression-free survival (PFS) and overall survival (OS). Thirteen out of 29 cases were CD10/BCL-6+/MUM-1+, being more frequent compared with systemic peripheral nodal lymphoma. Although post-germinal-center B-cell-originating PCNSLs (CD10/BCL-6/MUM-1+) showed a trend towards better response to MTX and progression-free survival than did germinal-center-related B-cell-originating PCNSLs (CD10+ OR CD10/BCL-6+/MUM-1+), the difference was only marginal (P = 0.04 Gehan–Breslow–Wilcoxon, P = 0.17 log-rank). Our results imply that different B-cell stages in PCNSL have significant relevance in terms of biological behavior. However, clinical use as a prognostic marker requires further investigation.

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References

  1. Jukich PJ, McCarthy BJ, Surawicz TS, Freels S, Davis FG (2001) Trends in incidence of primary brain tumors in the United States, 1985–1994. Neuro Oncol 3:141–151

    Article  CAS  PubMed  Google Scholar 

  2. Kadan-Lottick NS, Skluzacek MC, Gurney JG (2002) Decreasing incidence rates of primary central nervous system lymphoma. Cancer 95:193–202

    Article  PubMed  Google Scholar 

  3. Shibamoto Y, Ogino H, Suzuki G, Takemoto M, Araki N, Isobe K, Tsuchida E, Nakamura K, Kenjo M, Suzuki K, Hosono M, Tokumaru S, Ishihara S, Kato E, Ii N, Hayabuchi N (2008) Primary central nervous system lymphoma in Japan: changes in clinical features, treatment, and prognosis during 1985–2004. Neuro Oncol 10:560–568

    Article  PubMed  Google Scholar 

  4. Lin CH, Kuo KT, Chuang SS, Kuo SH, Chang JH, Chang KC, Hsu HC, Tien HF, Cheng AL (2006) Comparison of the expression and prognostic significance of differentiation markers between diffuse large B-cell lymphoma of central nervous system origin and peripheral nodal origin. Clin Cancer Res 12:1152–1156

    Article  CAS  PubMed  Google Scholar 

  5. Chang CC, McClintock S, Cleveland RP, Trzpuc T, Vesole DH, Logan B, Kajdacsy-Balla A, Perkins SL (2004) Immunohistochemical expression patterns of germinal center and activation B-cell markers correlate with prognosis in diffuse large B-cell lymphoma. Am J Surg Pathol 28:464–470

    Article  PubMed  Google Scholar 

  6. Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Muller-Hermelink HK, Campo E, Braziel RM, Jaffe ES, Pan Z, Farinha P, Smith LM, Falini B, Banham AH, Rosenwald A, Staudt LM, Connors JM, Armitage JO, Chan WC (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103:275–282

    Article  CAS  PubMed  Google Scholar 

  7. Braaten KM, Betensky RA, de Leval L, Okada Y, Hochberg FH, Louis DN, Harris NL, Batchelor TT (2003) BCL-6 expression predicts improved survival in patients with primary central nervous system lymphoma. Clin Cancer Res 9:1063–1069

    CAS  PubMed  Google Scholar 

  8. Levy O, Deangelis LM, Filippa DA, Panageas KS, Abrey LE (2008) Bcl-6 predicts improved prognosis in primary central nervous system lymphoma. Cancer 112:151–156

    Article  PubMed  Google Scholar 

  9. Wilson WH, Dunleavy K, Pittaluga S, Hegde U, Grant N, Steinberg SM, Raffeld M, Gutierrez M, Chabner BA, Staudt L, Jaffe ES, Janik JE (2008) Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol 26:2717–2724

    Article  CAS  PubMed  Google Scholar 

  10. Camilleri-Broet S, Criniere E, Broet P, Delwail V, Mokhtari K, Moreau A, Kujas M, Raphael M, Iraqi W, Sautes-Fridman C, Colombat P, Hoang-Xuan K, Martin A (2006) A uniform activated B-cell-like immunophenotype might explain the poor prognosis of primary central nervous system lymphomas: analysis of 83 cases. Blood 107:190–196

    Article  CAS  PubMed  Google Scholar 

  11. Chang CC, Kampalath B, Schultz C, Bunyi-Teopengco E, Logan B, Eshoa C, Dincer AP, Perkins SL (2003) Expression of p53, c-Myc, or Bcl-6 suggests a poor prognosis in primary central nervous system diffuse large B-cell lymphoma among immunocompetent individuals. Arch Pathol Lab Med 127:208–212

    PubMed  Google Scholar 

  12. Hiraga S, Arita N, Ohnishi T, Kohmura E, Yamamoto K, Oku Y, Taki T, Sato M, Aozasa K, Yoshimine T (1999) Rapid infusion of high-dose methotrexate resulting in enhanced penetration into cerebrospinal fluid and intensified tumor response in primary central nervous system lymphomas. J Neurosurg 91:221–230

    Article  CAS  PubMed  Google Scholar 

  13. Chu PG, Arber DA (2001) CD79: a review. Appl Immunohistochem Mol Morphol 9:97–106

    Article  CAS  PubMed  Google Scholar 

  14. Weiss LM, Arber DA, Strickler JG (1994) Nasal T-cell lymphoma. Ann Oncol 5(Suppl 1):39–42

    PubMed  Google Scholar 

  15. Sakamoto M, Oya N, Mizowaki T, Araki N, Nagata Y, Takayama K, Takahashi JA, Kano H, Katsuki T, Hashimioto N, Hiraoka M (2006) Initial experiences of palliative stereotactic radiosurgery for recurrent brain lymphomas. J Neurooncol 77:53–58

    Article  PubMed  Google Scholar 

  16. McAllister LD, Doolittle ND, Guastadisegni PE, Kraemer DF, Lacy CA, Crossen JR, Neuwelt EA (2000) Cognitive outcomes and long-term follow-up results after enhanced chemotherapy delivery for primary central nervous system lymphoma. Neurosurgery 46:51–60 (discussion 60–51)

    Article  CAS  PubMed  Google Scholar 

  17. Barrans SL, Carter I, Owen RG, Davies FE, Patmore RD, Haynes AP, Morgan GJ, Jack AS (2002) Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma. Blood 99:1136–1143

    Article  CAS  PubMed  Google Scholar 

  18. Niu H (2002) The proto-oncogene BCL-6 in normal and malignant B cell development. Hematol Oncol 20:155–166

    Article  PubMed  Google Scholar 

  19. Sanderson RD, Borset M (2002) Syndecan-1 in B lymphoid malignancies. Ann Hematol 81:125–135

    Article  CAS  PubMed  Google Scholar 

  20. Carbone A, Gloghini A, Larocca LM, Capello D, Pierconti F, Canzonieri V, Tirelli U, Dalla-Favera R, Gaidano G (2001) Expression profile of MUM1/IRF4, BCL-6, and CD138/syndecan-1 defines novel histogenetic subsets of human immunodeficiency virus-related lymphomas. Blood 97:744–751

    Article  CAS  PubMed  Google Scholar 

  21. Richter J, Ammerpohl O, Martin-Subero JI, Montesinos-Rongen M, Bibikova M, Wickham-Garcia E, Wiestler OD, Deckert M, Siebert R (2009) Array-based DNA methylation profiling of primary lymphomas of the central nervous system. BMC Cancer 9:455

    Article  PubMed  Google Scholar 

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Acknowledgements

This investigation was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan.

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Correspondence to Manabu Kinoshita.

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Kinoshita, M., Hashimoto, N., Izumoto, S. et al. Immunohistological profiling by B-cell differentiation status of primary central nervous system lymphoma treated by high-dose methotrexate chemotherapy. J Neurooncol 99, 95–101 (2010). https://doi.org/10.1007/s11060-010-0112-1

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  • DOI: https://doi.org/10.1007/s11060-010-0112-1

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