title: Protein expression of B-cell lymphoma gene 6 (BCL-6) in invasive breast cancer is associated with cyclin D1 and hypoxia-inducible factor-1alpha (HIF-1alpha).
abstract: B-cell lymphoma gene (BCL-6) upregulation contributes to immortalization of mouse embryo fibroblast and primary B cells via upregulation of cyclin D1. 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 (> or =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 D1 (r=0.197, P=0.016). Further, in chi2 analyses, BCL-6-positivity was associated with overexpression of p53 (P=0.016), and hypoxia-inducible factor-1alpha (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.
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Bos
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
authors.forename: Petra
authors.initials: P
authors.lastname: van der Groep
authors.forename: Astrid E
authors.initials: AE
authors.lastname: Greijer
authors.forename: Mario A J A
authors.initials: MA
authors.lastname: Hermsen
authors.forename: Ingrid
authors.initials: I
authors.lastname: Heijnen
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: Meijer
authors.forename: Jan P A
authors.initials: JP
authors.lastname: Baak
authors.forename: Herbert M
authors.initials: HM
authors.lastname: Pinedo
authors.forename: Elsken
authors.initials: E
authors.lastname: van der Wall
authors.forename: Avi
authors.initials: A
authors.lastname: Shvarts
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism; D044584:Carcinoma, Ductal / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; D019938:Cyclin D1