BCL-6 oncoprotein in breast cancer: loss of expression in disease progression.
OBJECTIVE
To investigate the biological role of BCL-6 oncoprotein in breast cancer disease progression (recurrence and metastasis).


METHODS
The series consisted of 93 consecutive female patients with primary breast cancer and median follow-up of 10 years. BCL-6 expression was assessed in vivo by immunohistochemistry and real-time PCR. Breast cancer cell lines and some metastasis-related genes (CXCR4, Itgbeta-3 and FLT-1) were also analysed by molecular techniques. Prognostic evaluation was performed by fitting a multivariate Cox regression model.


RESULTS
BCL-6 immunoexpression was positive in 22 (23.7%) tumours and negative in 71 (76.3%). All axillary lymph node metastases of 47 node-positive patients were negative, including 12 cases showing BCL-6-positive primary tumours. Likewise, in 9 recurrence cases, BCL-6 expression was similar or decreased compared with primary tumours. No correlation between immunoexpression and gene expression of BCL-6 was observed. BCL-6 was significantly reduced both in derived metastases of a breast cancer cell line (M435) and when the latter was treated with a demethylation agent (5-azacytidine). However, BCL-6-transfected breast cancer cell lines expressed significantly higher levels of CXCR4, Itgbeta-3 and FLT-1. Co-expression of the 4 genes was found in 4 of 17 tumours evaluated, but lacking prognostic significance. BCL-6 oncoprotein revealed no significant influence on outcome.


CONCLUSIONS
The results strongly suggest the loss of BCL-6 expression in breast cancer progression, which might be related with methylation status alterations of still unknown partner gene(s).
Pinto
António E
AE
Serviço de Anatomia Patológica, Instituto Português de Oncologia de Lisboa, E.P.E., Lisboa, Portugal. aepinto@ipolisboa.min-saude.pt
André
Saudade
S
Silva
Giovani
G
Vieira
Sara
S
Santos
Ana C
AC
Dias
Sérgio
S
Soares
Jorge
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D039661:Integrin beta3 / Q000096:biosynthesis / Q000235:genetics; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D051560:Proto-Oncogene Proteins c-bcl-6; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis / Q000235:genetics
C084103:BCL6 protein, human; D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; D004268:DNA-Binding Proteins; C061248:ITGB3 protein, human; D039661:Integrin beta3; D051560:Proto-Oncogene Proteins c-bcl-6; D019718:Receptors, CXCR4; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1