title: Fatty acid binding protein 7 expression and its sub-cellular localization in breast cancer.
abstract: FABP7 is a member of the multi-gene fatty acid binding protein family. It is expressed in the mammary gland and has been shown to function as inhibitor of proliferation of breast tumour cells and to promote differentiation through the JAK/Stat pathway. Cytoplasmic FABP7 expression has been shown to be associated with a favourable prognosis of basal-like breast cancer. In other tissues, varying sub-cellular localization of FABP7 between the nucleus and cytoplasm has been observed. Tissue microarray preparations of well-characterized series of 1,249 unselected and 245 ER-negative invasive breast cancers with a long-term follow-up were investigated in this study to assess the biological and clinical significance of FABP7 sub-cellular localization using immunohistochemistry. Both nuclear and cytoplasmic FABP7 were observed. Nuclear FABP7 was associated with high histologic grade, mitotic frequency, pleomorphism and stage, in addition to basal phenotype (BP) and triple-negative (TN) phenotype. Nuclear FABP7 expression showed an association with expression of markers associated with proliferation and cell-cycle control including Ki67, p53 and p21; however, cytoplasmic FABP7 was associated only with Ki67 and P53 (P = 0.001, < 0.001 respectively). Interestingly, in multivariate analysis, nuclear FABP7 expression in BP was significantly associated with longer DFI (P = 0.025) independent of cytoplasmic expression. Tumours with only nuclear positive FABP7 expression had significantly better prognosis than those with only cytoplasmic expression. This is the first study elucidating the sub-cellular localization of FABP7 in a large series of breast cancer cases. Our observations demonstrate the considerable heterogeneity in expression patterns of FABP7 within breast cancer that relates to differences in biological behaviour especially in basal-like breast cancer. Further investigation of the biology of FABP7 in breast cancer is warranted.
authors.affiliation: Department of Histopathology and School of Molecular Medical Sciences, The University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham City Hospital, Nottingham, UK. mrxaa31@nottingham.ac.uk
authors.forename: Alaa T
authors.initials: AT
authors.lastname: Alshareeda
authors.forename: Emad A
authors.initials: EA
authors.lastname: Rakha
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Nolan
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Green
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D015331:Cohort Studies; D003593:Cytoplasm / Q000378:metabolism; D018572:Disease-Free Survival; D000071438:Fatty Acid-Binding Protein 7; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D010641:Phenotype; D016016:Proportional Hazards Models; D021381:Protein Transport; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D025521:Tumor Suppressor Proteins