title: Prognostic impact of B-cell lymphoma 6 in primary CNS lymphoma.
abstract: BACKGROUND
  We investigated the prognostic significance of B-cell differentiation status and common B-cell differentiation markers in a post hoc analysis of 119 patients with primary CNS lymphoma (PCNSL) homogeneously receiving high-dose methotrexate (HDMTX)-based chemotherapy within the prospective G-PCNSL-SG1 trial.
  
  
  METHODS
  We evaluated protein expression of B-cell lymphoma 2 (BCL2), BCL6, CD10, and multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM1/IRF4) by immunohistochemistry and analyzed the association with survival.
  
  
  RESULTS
  The median follow-up of all patients was 67.5 months. Median progression-free survival (PFS) was 10.61 months (95% CI: 4.23-17.00). Median overall survival (OS) was 28.85 months (95% CI: 17.96-39.73). Eighty-nine tumors expressed BCL2 (92.7%), 24 (20.5%) expressed CD10, 60 (54.1%) expressed BCL6, and 87 (79.0%) expressed MUM1/IRF4. On the basis of the Hans algorithm, 80 tumors (73.4%) were classified to the non-germinal center B group, suggesting a post-germinal center origin of PCNSL. Expression of BCL6 (cutoff point 30%), but none of the other markers, was associated with shorter PFS (P = .047) and OS (P = .035). On multivariate analysis, BCL6 expression was associated with shorter PFS (hazard ratio: 1.95, 95% CI: 1.22-3.12, P = .005) but not OS (hazard ratio: 1.85, 95% CI: 0.71-4.80, P = .21). Classification according to Hans algorithm and expression status of the single B-cell markers BCL2, CD10, and MUM1/IRF4 did not correlate with prognosis.
  
  
  CONCLUSIONS
  The findings are limited by the fact that only 23% of all G-PCNSL-SG1 patients could be included in the analysis. If validated in an independent cohort, BCL6 may assume clinical relevance as an unfavorable prognostic biomarker in PCNSL.
authors: Department of Hematology and Oncology, Campus Benjamin Franklin, Charite Berlin, Berlin, Germany (S.K., F.S., E.T., A.K.); Institute of Pathology, Charite Berlin, Berlin, Germany (K.J.); Institute of Clinical Epidemiology and Applied Biostatistics, University Tuebingen, Tuebingen (P.M.); Institute of Neuropathology, University Bonn Medical Center, Brain Tumor Reference Center of the DGNN, Bonn, Germany (K.B., T.P.); Institute of Neuropathology, Charite Berlin, Berlin, Germany (J.R., F.H.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (P.R., M.W.).
authors: Stephan
authors: S
authors: Kreher
authors: Department of Hematology and Oncology, Campus Benjamin Franklin, Charite Berlin, Berlin, Germany (S.K., F.S., E.T., A.K.); Institute of Pathology, Charite Berlin, Berlin, Germany (K.J.); Institute of Clinical Epidemiology and Applied Biostatistics, University Tuebingen, Tuebingen (P.M.); Institute of Neuropathology, University Bonn Medical Center, Brain Tumor Reference Center of the DGNN, Bonn, Germany (K.B., T.P.); Institute of Neuropathology, Charite Berlin, Berlin, Germany (J.R., F.H.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (P.R., M.W.).
authors: Korinna
authors: K
authors: Jöhrens
authors: Department of Hematology and Oncology, Campus Benjamin Franklin, Charite Berlin, Berlin, Germany (S.K., F.S., E.T., A.K.); Institute of Pathology, Charite Berlin, Berlin, Germany (K.J.); Institute of Clinical Epidemiology and Applied Biostatistics, University Tuebingen, Tuebingen (P.M.); Institute of Neuropathology, University Bonn Medical Center, Brain Tumor Reference Center of the DGNN, Bonn, Germany (K.B., T.P.); Institute of Neuropathology, Charite Berlin, Berlin, Germany (J.R., F.H.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (P.R., M.W.).
authors: Felicitas
authors: F
authors: Strehlow
authors: Department of Hematology and Oncology, Campus Benjamin Franklin, Charite Berlin, Berlin, Germany (S.K., F.S., E.T., A.K.); Institute of Pathology, Charite Berlin, Berlin, Germany (K.J.); Institute of Clinical Epidemiology and Applied Biostatistics, University Tuebingen, Tuebingen (P.M.); Institute of Neuropathology, University Bonn Medical Center, Brain Tumor Reference Center of the DGNN, Bonn, Germany (K.B., T.P.); Institute of Neuropathology, Charite Berlin, Berlin, Germany (J.R., F.H.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (P.R., M.W.).
authors: Peter
authors: P
authors: Martus
authors: Department of Hematology and Oncology, Campus Benjamin Franklin, Charite Berlin, Berlin, Germany (S.K., F.S., E.T., A.K.); Institute of Pathology, Charite Berlin, Berlin, Germany (K.J.); Institute of Clinical Epidemiology and Applied Biostatistics, University Tuebingen, Tuebingen (P.M.); Institute of Neuropathology, University Bonn Medical Center, Brain Tumor Reference Center of the DGNN, Bonn, Germany (K.B., T.P.); Institute of Neuropathology, Charite Berlin, Berlin, Germany (J.R., F.H.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (P.R., M.W.).
authors: Kathrin
authors: K
authors: Borowiec
authors: Department of Hematology and Oncology, Campus Benjamin Franklin, Charite Berlin, Berlin, Germany (S.K., F.S., E.T., A.K.); Institute of Pathology, Charite Berlin, Berlin, Germany (K.J.); Institute of Clinical Epidemiology and Applied Biostatistics, University Tuebingen, Tuebingen (P.M.); Institute of Neuropathology, University Bonn Medical Center, Brain Tumor Reference Center of the DGNN, Bonn, Germany (K.B., T.P.); Institute of Neuropathology, Charite Berlin, Berlin, Germany (J.R., F.H.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (P.R., M.W.).
authors: Josefine
authors: J
authors: Radke
authors: Department of Hematology and Oncology, Campus Benjamin Franklin, Charite Berlin, Berlin, Germany (S.K., F.S., E.T., A.K.); Institute of Pathology, Charite Berlin, Berlin, Germany (K.J.); Institute of Clinical Epidemiology and Applied Biostatistics, University Tuebingen, Tuebingen (P.M.); Institute of Neuropathology, University Bonn Medical Center, Brain Tumor Reference Center of the DGNN, Bonn, Germany (K.B., T.P.); Institute of Neuropathology, Charite Berlin, Berlin, Germany (J.R., F.H.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (P.R., M.W.).
authors: Frank
authors: F
authors: Heppner
authors: Department of Hematology and Oncology, Campus Benjamin Franklin, Charite Berlin, Berlin, Germany (S.K., F.S., E.T., A.K.); Institute of Pathology, Charite Berlin, Berlin, Germany (K.J.); Institute of Clinical Epidemiology and Applied Biostatistics, University Tuebingen, Tuebingen (P.M.); Institute of Neuropathology, University Bonn Medical Center, Brain Tumor Reference Center of the DGNN, Bonn, Germany (K.B., T.P.); Institute of Neuropathology, Charite Berlin, Berlin, Germany (J.R., F.H.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (P.R., M.W.).
authors: Patrick
authors: P
authors: Roth
authors: Department of Hematology and Oncology, Campus Benjamin Franklin, Charite Berlin, Berlin, Germany (S.K., F.S., E.T., A.K.); Institute of Pathology, Charite Berlin, Berlin, Germany (K.J.); Institute of Clinical Epidemiology and Applied Biostatistics, University Tuebingen, Tuebingen (P.M.); Institute of Neuropathology, University Bonn Medical Center, Brain Tumor Reference Center of the DGNN, Bonn, Germany (K.B., T.P.); Institute of Neuropathology, Charite Berlin, Berlin, Germany (J.R., F.H.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (P.R., M.W.).
authors: Eckhard
authors: E
authors: Thiel
authors: Department of Hematology and Oncology, Campus Benjamin Franklin, Charite Berlin, Berlin, Germany (S.K., F.S., E.T., A.K.); Institute of Pathology, Charite Berlin, Berlin, Germany (K.J.); Institute of Clinical Epidemiology and Applied Biostatistics, University Tuebingen, Tuebingen (P.M.); Institute of Neuropathology, University Bonn Medical Center, Brain Tumor Reference Center of the DGNN, Bonn, Germany (K.B., T.P.); Institute of Neuropathology, Charite Berlin, Berlin, Germany (J.R., F.H.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (P.R., M.W.).
authors: Torsten
authors: T
authors: Pietsch
authors: Department of Hematology and Oncology, Campus Benjamin Franklin, Charite Berlin, Berlin, Germany (S.K., F.S., E.T., A.K.); Institute of Pathology, Charite Berlin, Berlin, Germany (K.J.); Institute of Clinical Epidemiology and Applied Biostatistics, University Tuebingen, Tuebingen (P.M.); Institute of Neuropathology, University Bonn Medical Center, Brain Tumor Reference Center of the DGNN, Bonn, Germany (K.B., T.P.); Institute of Neuropathology, Charite Berlin, Berlin, Germany (J.R., F.H.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (P.R., M.W.).
authors: Michael
authors: M
authors: Weller
authors: Department of Hematology and Oncology, Campus Benjamin Franklin, Charite Berlin, Berlin, Germany (S.K., F.S., E.T., A.K.); Institute of Pathology, Charite Berlin, Berlin, Germany (K.J.); Institute of Clinical Epidemiology and Applied Biostatistics, University Tuebingen, Tuebingen (P.M.); Institute of Neuropathology, University Bonn Medical Center, Brain Tumor Reference Center of the DGNN, Bonn, Germany (K.B., T.P.); Institute of Neuropathology, Charite Berlin, Berlin, Germany (J.R., F.H.); Department of Neurology, University Hospital Zurich, Zurich, Switzerland (P.R., M.W.).
authors: Agnieszka
authors: A
authors: Korfel
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016543:Central Nervous System Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D005260:Female; D006801:Humans; D050835:Interferon Regulatory Factors / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D016393:Lymphoma, B-Cell / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000378:metabolism; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000378:metabolism*; D000099218:Interferon Regulatory Factor-4
chemical_list: D015415:Biomarkers; D050835:Interferon Regulatory Factors; D015260:Neprilysin; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D000099218:Interferon Regulatory Factor-4
keywords: BCL-6; GCB; PCNSL; non-GCB; survival