title: BCL-6 expression predicts improved survival in patients with primary central nervous system lymphoma.
abstract: OBJECTIVE
  The purpose of this study was to investigate the histogenetic origin of primary central nervous system lymphoma (PCNSL) with respect to stage of B-cell differentiation and to identify prognostic markers in a cohort of patients with PCNSL treated with i.v. high-dose methotrexate therapy.
  
  
  METHODS
  This study included 33 patients with PCNSL treated with high-dose i.v. methotrexate at the Massachusetts General Hospital for whom archival tumor tissue was available. All 33 patients tested negative for HIV. The lymphomas were morphologically subclassified according to the Kiel system, as modified in the WHO classification. Immunohistochemistry for the following antigens was performed: BCL-6; BCL-2; MUM1; CD10; vs38c; CD138; CD44; p16; and p53. Fluorescence in situ hybridization and multiplex PCR for CDKN2A/p16 were also performed.
  
  
  RESULTS
  There were 17 women and 16 men enrolled, with a median age of 60 years. All tumors were diffuse large B-cell lymphomas. Of the 23 cases that could be subclassified, 22 were centroblastic, and 1 was immunoblastic. Twenty-six of 33 tumors were BCL-6+, 6 of 32 tumors were CD10+, 27 of 29 tumors were BCL-2+, 31 of 32 tumors were MUM1+, 11 of 31 tumors were CD44+, 4 of 33 tumors were vs38c+, and 0 of 32 tumors were CD138+. There were 18 of 32 (56%) complete responses and 8 of 32 (25%) partial responses to methotrexate, whereas 6 of 33 (18%) progressed during treatment. Ten patients died of disease. Expression of BCL-6 was significantly associated with longer overall survival (P = 0.002; median survival, 101 versus 14.7 months, with approximately 95% lower confidence limits of 41.7 and 8.8 months, respectively).
  
  
  CONCLUSIONS
  In this group of 33 patients with PCNSL, expression of BCL-6 was significantly associated with longer overall survival. BCL-6 warrants further investigation as a potentially important prognostic marker in this disease.
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Braaten
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Betensky
authors.forename: Laurence
authors.initials: L
authors.lastname: de Leval
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Okada
authors.forename: Fred H
authors.initials: FH
authors.lastname: Hochberg
authors.forename: David N
authors.initials: DN
authors.lastname: Louis
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Harris
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Batchelor
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D002454:Cell Differentiation; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D050835:Interferon Regulatory Factors; D008223:Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D015260:Neprilysin / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011509:Proteoglycans / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051560:Proto-Oncogene Proteins c-bcl-6; D053668:Syndecan-1; D053667:Syndecans; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D000099218:Interferon Regulatory Factor-4
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D018960:Hyaluronan Receptors; D050835:Interferon Regulatory Factors; D008562:Membrane Glycoproteins; D008727:Methotrexate; D015260:Neprilysin; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D053668:Syndecan-1; D053667:Syndecans; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D000099218:Interferon Regulatory Factor-4; C508241:SDC1 protein, human