Expression of the forkhead box transcription factor FOXP1 is associated with estrogen receptor alpha, estrogen receptor beta and improved survival in familial breast cancers.

Abstract

Aims: The role of FOXP1 in sporadic breast cancers have been widely studied but its role in familial breast cancers is yet unexplored. The aims of this study were to investigate FOXP1 expression in different molecular subtypes of familial breast cancers and to correlate its expression with clinicopathological parameters, estrogen receptors (ER) and survival.

Methods: We performed immunohistochemical staining for FOXP1 on tissue microarrays in 126 familial breast carcinomas comprising 35 BRCA1, 34 BRCA2 and 57 BRCAX.

Results: Nuclear FOXP1 expression in familial breast cancers ranged from focal weak to widespread strong expression. Expression of FOXP1 was significantly higher in familial breast cancers as a combined group (54%) compared with sporadic cancers (46%) (p<0.001). There was a significant correlation between FOXP1 with ERα (p=0.038) and ERß (p=0.007) in familial breast cancers. FOXP1 was more highly expressed in familial breast cancers as a combined group 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 as a group. 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).

Conclusion: This data suggest 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.