title: Expression of the FOXP1 transcription factor is strongly associated with inferior survival in patients with diffuse large B-cell lymphoma.
abstract: Gene expression profiling studies have reported up-regulated mRNA expression of the FOXP1 forkhead transcription factor in response to normal B-cell activation and high expression in a poor prognosis subtype of diffuse large B-cell lymphoma (DLBCL). The purpose of this study was to investigate the prognostic importance of FOXP1 protein expression in an independent series of DLBCL.First, the specificity of our FOXP1 monoclonal antibody was verified by confirming that it did not recognize the closely related FOXP2, FOXP3, or FOXP4 proteins. FOXP1 protein expression was then analyzed by immunohistochemistry using a DLBCL tissue microarray constructed from 101 previously untreated de novo cases from the British Columbia Cancer Agency. FOXP1 expression was scored as either positive (>30% positive nuclei) or negative (<30% positive nuclei). The overall survival curves clearly showed that patients grouped as FOXP1-positive (40%) had a significantly decreased overall survival (P = 0.0001). FOXP1-positive patients had a median overall survival of 1.6 years compared with 12.2 years in FOXP1-negative cases. In addition, FOXP1-positive patients showed a clear trend to earlier progression in comparison to the FOXP1-negative patients. The analysis of FOXP1 expression within low, medium, and high International Prognostic Index groupings found that FOXP1-negative patients had better overall survival within each group indicating that FOXP1 expression has predictive value independent of the International Prognostic Index subgrouping, a finding that was confirmed in multivariate analysis. These initial results suggest that FOXP1 expression may be important in DLBCL pathogenesis.
authors.affiliation: Leukemia Research Fund Immunodiagnostics Unit, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DU, United Kingdom. alison.banham@ndcls.ox.ac.uk
authors.forename: Alison H
authors.initials: AH
authors.lastname: Banham
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Brown
authors.forename: Jacqueline L
authors.initials: JL
authors.lastname: Cordell
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: Gayatri
authors.initials: G
authors.lastname: Sreenivasan
authors.forename: Pedro
authors.initials: P
authors.lastname: Farinha
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Horsman
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000918:Antibody Specificity; D019556:COS Cells; D002522:Chlorocebus aethiops; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010957:Plasmids / Q000235:genetics; D011379:Prognosis; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D016019:Survival Analysis; D046888:Tissue Array Analysis; D014162:Transfection
chemical_list: D018076:DNA, Complementary; C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D012097:Repressor Proteins