Expression of the forkhead box transcription factor F0XP1 is associated with oestrogen receptor alpha,oestrogen receptor beta and improved survival in familial breast cancers

摘要

Background: The role of F0XP1 in sporadic breast cancers has been widely studied but its role in familial breast cancers is yet unexplored. Aims: To investigate F0XP1 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 F0XP1 was performed in 126 familial breast carcinomas comprising 35 BRCA1, 34 BRCA2 and 57 BRCAX. Results: Nuclear F0XP1 expression ranged from focal weak to widespread strong expression. Expression of F0XP1 was higher in familial breast cancers (54%) compared with sporadic cancers (46%) (p<0.001). There was a significant correlation between F0XP1 with ERa (p = 0.038) and ERβ (p = 0.007) in familial breast cancers. F0XP1 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 F0XP1 expression was associated with a shorter relapse-free (p = 0.025) and overall survival (p = 0.009) in familial breast cancer. Negativity for F0XP1 was associated with a significantly worse overall survival in BRCA2 cancers (p = 0.021) and there was a nonsignificant separation of the survival curves for BRCA1 cancers (p = 0.183). No differences in survival were seen for BRCAX cancers (p = 0.762). Conclusion: Results suggest that F0XP1 demonstrates different expression patterns in familial breast cancers than sporadic tumours, even in tumours showing similar phenotypes. They also suggest a different role of F0XP1 as a tumour suppressor in familial tumours, which is unrelated to ER expression and may impact on therapeutic options.