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01-07-2012 | Preclinical Study

Fatty acid binding protein 7 expression and its sub-cellular localization in breast cancer

Authors: Alaa T. Alshareeda, Emad A. Rakha, Christopher C. Nolan, Ian O. Ellis, Andrew R. Green

Published in: Breast Cancer Research and Treatment | Issue 2/2012

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.

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Title: Fatty acid binding protein 7 expression and its sub-cellular localization in breast cancer
Authors: Alaa T. Alshareeda
Emad A. Rakha
Christopher C. Nolan
Ian O. Ellis
Andrew R. Green
Publication date: 01-07-2012
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 2/2012
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-012-2083-8

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