title: Prognostic value of immunohistochemical profile and response to high-dose methotrexate therapy in primary CNS lymphoma.
abstract: Several biomarkers have been identified as prognostic factors in primary central nervous system lymphoma (PCNSL). However, the correlation between the histogenetic origin of PCNSL and the response to therapy is still unclear. To elucidate the utility of immunophenotypic markers in predicting clinical outcomes, we investigated 27 immunocompetent patients with PCNSL treated with high-dose methotrexate therapy. Of the 27 patients, 25 received whole-brain radiotherapy after high-dose methotrexate. Immunostaining for CD5, CD10, BCL-6, and MUM-1 was used to determine the immunophenotypic profile of diffuse large B-cell lymphoma of PCNSL. We then evaluated whether immunophenotypic markers were associated with the response to therapy or patients' survival. The response to induction high-dose methotrexate therapy was determined by magnetic resonance imaging after three courses of i.v. high-dose methotrexate. We categorized B-cell lymphomas into three known subtypes: germinal center B-cell (GCB), activated-GCB, and post-GCB subtypes according to immunohistochemical profile. All the BCL-6-positive samples were co-positive for MUM-1 and therefore classified into activated-GCB subtype. BCL-6 expression in this study was associated with poor progression-free survival (P = 0.038). No immunophenotypic markers or subtypes had a significant effect on the response to high-dose methotrexate therapy. However, the response itself was a significant predictor for both progression-free survival (P < 0.001) and overall survival (P = 0.003). Further investigation is needed to assess BCL-6 as a potential prognostic factor in PCNSL.
authors.affiliation: Department of Neurosurgery, Nagoya University, Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. momota-nsu@umin.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Momota
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Narita
authors.forename: Akiko M
authors.initials: AM
authors.lastname: Maeshima
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Miyakita
authors.forename: Aya
authors.initials: A
authors.lastname: Shinomiya
authors.forename: Takashi
authors.initials: T
authors.lastname: Maruyama
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Muragaki
authors.forename: Soichiro
authors.initials: S
authors.lastname: Shibui
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D016543:Central Nervous System Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000188:drug therapy*; D004268:DNA-Binding Proteins / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D050835:Interferon Regulatory Factors / Q000378:metabolism; D008223:Lymphoma / Q000145:classification / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D051560:Proto-Oncogene Proteins c-bcl-6; D016019:Survival Analysis; D013997:Time Factors; D000099218:Interferon Regulatory Factor-4
chemical_list: D015703:Antigens, CD; D004268:DNA-Binding Proteins; D007166:Immunosuppressive Agents; D050835:Interferon Regulatory Factors; D008727:Methotrexate; D051560:Proto-Oncogene Proteins c-bcl-6; D000099218:Interferon Regulatory Factor-4; C084103:BCL6 protein, human