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Detection of germinal center B-cell lymphoma in archival specimens: critical evaluation of Bcl-6 protein expression in diffuse large B-cell lymphoma of the tonsil.

Abstract
Expression of Bcl-6 and CD10, markers for the tumor of the germinal center (GC) B-cell derivation, has been studied in primary diffuse large B-cell lymphomas (DLBCLs) of the lymph node, gastrointestinal tract, and mediastinum. In these studies, the coexpression rate of CD10 and Bcl-6 was relatively constant at 30% approximately 40%, but the frequency of Bcl-6+ tumors varied from 55% to 100%, raising doubts about the usefulness of Bcl-6 expression in identifying the tumor of GC B-cell derivation. Because the expression of Bcl-6 in tumors of non-GC B-cell origin has recently been reported, we critically evaluated the expression of Bcl-6 and CD10 in primary DLBCLs of the tonsil, a relatively common tumor in Japan and Korea. The cases (n = 51) represented a consecutive series for any recent 2-year period at several teaching hospitals in Korea and Japan. Formalin-fixed, paraffin-embedded specimens were used for immunostaining. Staining for Bcl-6 and CD10 was positive in 44 (86%) and 22 cases (45%), respectively. However, among those positive for Bcl-6 (>10% Bcl-6+ tumor cells), 2 basic patterns were recognized: uniform and nonuniform. The uniform pattern was characterized by a dense population (>75%) and a consistent density in any given area, resembling the staining pattern observed in GC or follicular lymphoma (FL) (the "GC/FL" pattern). In contrast, the nonuniform pattern exhibited a varying density from area to area, as well as a less-dense population (<75%). The uniform pattern was observed in 26 cases (51%). All but 1 (95%) of the CD10+ tumors coexpressed Bcl-6, with most (82%) displaying the uniform pattern. We conclude that tumors showing a uniform pattern of Bcl-6 expression should be distinguished from those showing a nonuniform pattern, because the former most likely represent tumors of GC B-cell derivation and the latter most likely represent tumors of non-GC derivation. GC B-cell lymphoma thus defined accounted for 51% of tonsillar DLBCL, a proportion comparable to that of the nodal DLBCL. CD10 expression correlated with the "GC/FL" pattern, but appeared to be not essential for the identification of GC B-cell lymphoma. This study suggests that a significant proportion of tonsillar DLBCLs in Asia is of GC B-cell origin rather than of mucosa-associated lymphoid tissue origin. This finding may have significance for clinical management of these lymphomas.
AuthorsHowe J Ree, Koichi Ohsima, Katsuyuki Aozasa, Kengo Takeuchi, Chul Woo Kim, Woo Ick Yang, Joor Yung Huh, Seung-Sook Lee, Yong-Hye Ko, Mi Seon Kwon, Eun Yoon Cho, Yoon-La Choi, Jong Chul Rhee, Masahiro Kikuchi, Shigeo Mori
JournalHuman pathology (Hum Pathol) Vol. 34 Issue 6 Pg. 610-6 (Jun 2003) ISSN: 0046-8177 [Print] United States
PMID12827616 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • Transcription Factors
  • Neprilysin
Topics
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Archives
  • Biomarkers, Tumor (metabolism)
  • Child
  • DNA-Binding Proteins (metabolism)
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Germinal Center (metabolism, pathology)
  • Humans
  • Lymphoma, B-Cell (metabolism, pathology)
  • Lymphoma, Large B-Cell, Diffuse (metabolism, pathology)
  • Male
  • Middle Aged
  • Neprilysin (metabolism)
  • Proto-Oncogene Proteins (metabolism)
  • Proto-Oncogene Proteins c-bcl-6
  • Tonsillar Neoplasms (metabolism, pathology)
  • Transcription Factors (metabolism)

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