Protein expression of B-cell lymphoma gene 6 (BCL-6) in invasive breast cancer is associated with cyclin D1 and hypoxia-inducible factor-1α (HIF-1α)

Reinhard Bos, Paul J. Van Diest, Petra Van Der Groep, Astrid E. Greijer, Mario A.J.A. Hermsen, Ingrid Heijnen, Gerrit A. Meijer, Jan P.A. Baak, Herbert M. Pinedo, Elsken Van Der Wall, Avi Shvarts

Research output: Contribution to journalArticlepeer-review


B-cell lymphoma gene (BCL-6) upregulation contributes to immortalization of mouse embryo fibroblast and primary B cells via upregulation of cyclin D 1. As cyclin D1 overexpression is a common phenomenon in different cancers, BCL-6 protein overexpression may not be restricted to lymphomas. In this study, expression of BCL-6 was investigated by immunohistochemistry on paraffin-embedded specimens from 150 breast cancer patients and 10 specimens of normal breast tissue. The results showed BCL-6 overexpression (≥ 10% of cells) in 24/150 (16%) breast cancer patients, whereas in normal breast low expression (<1%) of BCL-6 was observed. In linear regression analysis BCL-6 expression was associated with cyclin D 1 (r = 0.197, P = 0.016). Further, in χ2 analyses, BCL-6-positivity was associated with over-expression of p53 (P = 0.016), and hypoxia-inducible factor-1α (P< 0.001). Involvement of BCL-6 in breast carcinogenesis is further underscored by comparative genomic hybridization analysis that showed gains at the BCL-6 locus (3q27) in 14/86 (16%) breast cancer tissues. The cases with amplification in BCL-6 showed an increased (25%) incidence of BCL-6 protein overexpression. Thus, this study is the first to show that BCL-6 oncogene activation plays a role in cancers other than lymphomas.

Original languageEnglish (US)
Pages (from-to)8948-8951
Number of pages4
Issue number55
StatePublished - Dec 4 2003


  • BCL-6
  • Breast cancer
  • Cyclin D
  • HIF-1α
  • Oncogenes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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