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.

CONTEXT Primary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) in immunocompetent individuals, although rare, has been rising in incidence. Currently, no reliable prognostic markers are available for these individuals. OBJECTIVE To study the implications of expression of a panel of oncogenic proteins (Bcl-2, Bcl-6, and c-Myc) and p53 for predicting clinical outcome, particularly overall survival, in immunocompetent individuals with primary CNS DLBCL. DESIGN Fourteen primary CNS DLBCL cases were retrospectively studied by immunohistochemistry on formalin-fixed, paraffin-embedded sections for the expression of c-Myc, Bcl-2, Bcl-6, and p53. RESULTS The overall frequencies of expression for p53, c-Myc, Bcl-2, and Bcl-6 in these cases were 29%, 50%, 71%, and 57%, respectively. Cases with expression of p53, c-Myc, or Bcl-6 had a poorer overall survival than those without (Kaplan-Meier survival analysis: 50% cumulative overall survival, 2 months vs 30-60 months, P =.02, log-rank test; 9-16 months vs 21-60 months, P =.03, log-rank test; and 9-16 months vs 21-60 months, P =.16, log-rank test, respectively). The expression of Bcl-2 or proliferation activity by MIB-1 showed no correlation with overall survival. Likewise, the clinical parameters, including age, location of tumors, multiplicity of tumor lesions, and lactase dehydrogenase levels revealed no impact on overall survival. CONCLUSION Our results suggest that patients with expression of p53, c-Myc, or Bcl-6 have a poorer overall survival than those without. Since traditional prognostic markers in non-CNS DLBCL, such as staging and International Prognostic Index scores, are not applicable to primary CNS DLBCL, evaluation of p53, c-Myc, and Bcl-6 by immunohistochemistry may be warranted as part of prognostic evaluation in immunocompetent patients with primary CNS DLBCL. Further studies are indicated to confirm our observations.

[1]  D. Longo,et al.  p53 mutation is associated with progression in follicular lymphomas. , 1993, Blood.

[2]  T. Hsieh,et al.  Apoptosis and restriction of G(1)/S cell cycle by fenretinide in Burkitt's lymphoma mutu I cell line accessed with bcl-6 down-regulation. , 2000, Biochemical and biophysical research communications.

[3]  F. d'Amore,et al.  Primary central nervous system lymphomas in immunocompetent individuals: histology, Epstein-Barr virus genome, Ki-67 proliferation index, p53 and bcl-2 gene expression. , 1998, Leukemia & lymphoma.

[4]  Ellen,et al.  Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin's lymphomas: a prospective Southwest Oncology Group trial. , 1994, Blood.

[5]  D. Longo,et al.  MYC rearrangements in histologically progressed follicular lymphomas. , 1992, Blood.

[6]  G. Jh,et al.  Primary malignant non-Hodgkin's lymphoma of the central nervous system. , 1987, Pathology annual.

[7]  K. Ohshima,et al.  Prognostic clinicopathologic factors, including immunologic expression in diffuse large B‐cell lymphomas , 1999, Pathology international.

[8]  Elaine S. Jaffe,et al.  A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. , 1994, Blood.

[9]  H. Stein,et al.  Differential expression of apoptosis, Bcl‐x and c‐Myc in normal and malignant lymphoid tissues , 1997, European journal of haematology.

[10]  L. Xerri,et al.  What's new in primary central nervous system lymphomas? , 1990, Pathology, research and practice.

[11]  L. Larocca,et al.  The molecular and phenotypic profile of primary central nervous system lymphoma identifies distinct categories of the disease and is consistent with histogenetic derivation from germinal center-related B cells. , 1998, Blood.

[12]  J. Cigudosa,et al.  Chromosomal and gene amplification in diffuse large B-cell lymphoma. , 1998, Blood.

[13]  P. Bailey INTRACRANIAL SARCOMATOUS TUMORS OF LEPTOMENINGEAL ORIGIN , 1929 .

[14]  S. Swerdlow,et al.  Immunophenotypic and Genotypic Markers of Follicular Center Cell Neoplasia in Diffuse Large B-Cell Lymphomas , 2000, Modern Pathology.

[15]  R Tibshirani,et al.  Expression of a single gene, BCL-6, strongly predicts survival in patients with diffuse large B-cell lymphoma. , 2001, Blood.

[16]  H. Abe,et al.  Expression of oncogenic molecules in primary central nervous system lymphomas in immunocompetent patients , 1998, Acta Neuropathologica.

[17]  O. Wiestler,et al.  Apoptosis and apoptosis-related gene products in primary non-Hodgkin’s lymphoma of the central nervous system , 1998, Acta Neuropathologica.

[18]  S. Perkins,et al.  Expression of c-Myc and p53 correlates with clinical outcome in diffuse large B-cell lymphomas. , 2000, American journal of clinical pathology.

[19]  F. d'Amore,et al.  Clinicopathological features, survival and prognostic factors of primary central nervous system lymphomas: trends in incidence of primary central nervous system lymphomas and primary malignant brain tumors in a well-defined geographical area. Population-based data from the Danish Lymphoma Registry, , 1995, Leukemia & lymphoma.

[20]  P. Burger,et al.  Increasing incidence of primary brain lymphoma in the US , 1988, Cancer.

[21]  M. Piris,et al.  p53 expression in non-Hodgkin's lymphomas: a marker of p53 inactivation? , 1995, Leukemia & lymphoma.

[22]  S. Blasius,et al.  Primary non-Hodgkin lymphomas of the CNS-proliferation, oncoproteins and Epstein-Barr-virus. , 1996, General & diagnostic pathology.