title: Expression of the forkhead box transcription factor FOXP1 is associated with oestrogen receptor alpha, oestrogen receptor beta and improved survival in familial breast cancers.
abstract: BACKGROUND
  The role of FOXP1 in sporadic breast cancers has been widely studied but its role in familial breast cancers is yet unexplored.
  
  
  OBJECTIVE
  To investigate FOXP1 expression in different molecular subtypes of familial breast cancers and to correlate its expression with clinicopathological parameters, oestrogen receptors (ER) and survival.
  
  
  METHODS
  Immunohistochemical staining for FOXP1 was performed in 126 familial breast carcinomas comprising 35 BRCA1, 34 BRCA2 and 57 BRCAX.
  
  
  RESULTS
  Nuclear FOXP1 expression ranged from focal weak to widespread strong expression. Expression of FOXP1 was higher in familial breast cancers (54%) compared with sporadic cancers (46%) (p<0.001). There was a significant correlation between FOXP1 with ERalpha (p = 0.038) and ERbeta (p = 0.007) in familial breast cancers. FOXP1 was more highly expressed in familial breast cancers compared with sporadic cancers for luminal (p = 0.021) and basal (p<0.001), but not HER2 and null phenotypes (both p>0.05). The absence of FOXP1 expression was associated with a shorter relapse-free (p = 0.025) and overall survival (p = 0.009) in familial breast cancer. Negativity for FOXP1 was associated with a significantly worse overall survival in BRCA2 cancers (p = 0.021) and there was a non-significant separation of the survival curves for BRCA1 cancers (p = 0.183). No differences in survival were seen for BRCAX cancers (p = 0.762).
  
  
  CONCLUSIONS
  Results suggest that FOXP1 demonstrates different expression patterns in familial breast cancers than sporadic tumours, even in tumours showing similar phenotypes. They also suggest a different role of FOXP1 as a tumour suppressor in familial tumours, which is unrelated to ER expression and may impact on therapeutic options.
authors.affiliation: Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Rayoo
authors.forename: M
authors.initials: M
authors.lastname: Yan
authors.forename: E A
authors.initials: EA
authors.lastname: Takano
authors.forename: G J
authors.initials: GJ
authors.lastname: Bates
authors.forename: P J
authors.initials: PJ
authors.lastname: Brown
authors.forename: A H
authors.initials: AH
authors.lastname: Banham
authors.forename: S B
authors.initials: SB
authors.lastname: Fox
mesh_terms: D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins; D019313:BRCA1 Protein / Q000378:metabolism; D024682:BRCA2 Protein / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D010641:Phenotype; D011379:Prognosis; D012097:Repressor Proteins / Q000378:metabolism*; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D009363:Neoplasm Proteins; D012097:Repressor Proteins