title: Immunohistological profiling by B-cell differentiation status of primary central nervous system lymphoma treated by high-dose methotrexate chemotherapy.
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.
authors.affiliation: Department of Neurosurgery, Osaka University Gradate School of Medicine, 2-2 Yamadoka, Suita, Osaka 565-0871, Japan. m-kinoshita@nsurg.med.osaka-u.ac.jp
authors.forename: Manabu
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Naoya
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Shuichi
authors.initials: S
authors.lastname: Izumoto
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Okita
authors.forename: Naoki
authors.initials: N
authors.lastname: Kagawa
authors.forename: Motohiko
authors.initials: M
authors.lastname: Maruno
authors.forename: Takanori
authors.initials: T
authors.lastname: Ohnishi
authors.forename: Norio
authors.initials: N
authors.lastname: Arita
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yoshimine
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000187:drug effects*; D051925:CD79 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D050835:Interferon Regulatory Factors / Q000378:metabolism; D008223:Lymphoma / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008727:Methotrexate / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D015260:Neprilysin / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D012189:Retrospective Studies; D053668:Syndecan-1 / Q000378:metabolism; D000099218:Interferon Regulatory Factor-4
chemical_list: D051925:CD79 Antigens; D004268:DNA-Binding Proteins; D007166:Immunosuppressive Agents; D050835:Interferon Regulatory Factors; D008727:Methotrexate; D015260:Neprilysin; D051560:Proto-Oncogene Proteins c-bcl-6; D053668:Syndecan-1; D000099218:Interferon Regulatory Factor-4; C084103:BCL6 protein, human; C497881:CD79A protein, human; C508241:SDC1 protein, human