Diffuse large B-cell lymphoma with extra Bcl-2 gene signals detected by FISH analysis is associated with a "non-germinal center phenotype"

Shigeru Kusumoto, Yukio Kobayashi, Naohiro Sekiguchi, Kazuki Tanimoto, Yasushi Onishi, Yukiko Yokota, Takashi Watanabe, Akiko Miyagi Maeshima, Takashi Ishida, Hiroshi Inagaki, Yoshihiro Matsuno, Ryuzo Ueda, Kensei Tobinai

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Amplification and translocation of the Bcl-2 gene has been detected in a certain subset of diffuse large B-cell lymphomas (DLBCL). The correlations among Bcl-2 protein expression, gene translocation or amplification, and the molecular signature determined by cDNA array are poorly understood. This study examined 25 cases with de novo nodal DLBCL. Interphase fluorescence in situ hybridization (FISH) analysis was performed to evaluate the Bcl-2 gene using IGH/BCL2 and CEP18 centromere probes (Vysis). When extra Bcl-2 gene signals were observed in each tumor cell and when these signals were in proportion to the extra CEP18 probe signals, we regarded the findings as indicating the presence of an additional chromosome 18; when extra Bcl-2 signals were observed but additional CEP18 signals were not, we regarded the findings as indicating the presence of gene amplification. A panel of 3 antigens (CD10, Bcl-6, and MUM-1) was applied to categorize each case as either a "germinal center B-cell (GCB) phenotype" or a "non-GCB phenotype." Of the 25 cases examined, 8 cases (32%) were classified as "GCB phenotype" and 17 cases (68%) were classified as "non-GCB phenotype." A FISH analysis revealed that t(14;18) was detected in 2 of the 8 cases (25%) with the "GCB phenotype" but in none of the 17 "non-GCB phenotype" cases. Extra Bcl-2 gene signals were detected in 7 of the 25 (28%) cases examined: n = 5 for an additional chromosome 18, n = 1 for gene amplification, and n = 1 for additional chromosome 18 + gene amplification. Extra Bcl-2 gene signals were exclusively detected in DLBCL with the "non-GCB phenotype"; these cases, with the exception of one, stained strongly positive for Bcl-2. The DLBCLs with Bcl-2 protein over-expression were classified into at least two heterogeneous molecular groups, based on the results of the FISH analysis.

Original languageEnglish
Pages (from-to)1067-1073
Number of pages7
JournalAmerican Journal of Surgical Pathology
Volume29
Issue number8
Publication statusPublished - 2005 Aug 1
Externally publishedYes

Keywords

  • DLBCL
  • FISH
  • Gene amplification
  • t(14;18)

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

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