Overexpression of TFAP2C in invasive breast cancer correlates with a poorer response to anti-hormone therapy and reduced patient survival

Gee, Julia Margaret Wendy ORCID: https://orcid.org/0000-0001-6483-2015, Eloranta, J. J., Ibbitt, J. C., Robertson, J. F. R., Ellis, I. O., Williams, T., Nicholson, Robert Ian and Hurst, H. C. 2009. Overexpression of TFAP2C in invasive breast cancer correlates with a poorer response to anti-hormone therapy and reduced patient survival. The Journal of Pathology 217 (1) , pp. 32-41. 10.1002/path.2430

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Abstract

The AP-2 transcription factor encoded by the TFAP2C gene is a member of a family of homologous DNA binding proteins that play essential roles during vertebrate embryogenesis but show a restricted pattern of expression in the adult. Elevated expression of the AP-2 and AP-2 family members has been associated with a number of neoplasms, particularly breast cancer. Here we present an exploratory immunohistochemical study of an archival primary breast tumour series (n = 75) with parallel clinicopathological data using a new, well-characterized antibody to AP-2. Heterogeneous, exclusively nuclear expression of AP-2 was found in the epithelial and myoepithelial compartments of normal breast and within tumour epithelial cells. In the breast cancer series, the most notable association was a correlation between elevated levels of AP-2 and shortened patient survival (p = 0.0009*). This relationship was also conserved in ER-positive and ErbB2-negative patients; sub-groups generally considered to have a relatively good prognosis. When patient data for survival and duration of treatment response on anti-hormone therapy were examined by multivariate analysis, AP-2 was revealed in this study to be an independent predictor of outcome for both survival (p = 0.005) and response to anti-hormone therapy (p = 0.046). Studies using in vitro models confirmed that while tamoxifen response is associated with lower levels of AP-2, acquisition of resistance to this and other anti-hormone measures (eg faslodex or oestrogen deprivation) is associated with high levels of nuclear AP-2. Together these data suggest that elevated tumour AP-2 expression can contribute to the failure of cells to growth arrest following anti-hormone treatment and lead to sustained growth and poorer patient outcome.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	AP-2 transcription factors ; breast cancer ; tamoxifen resistance ; prognostic markers ; immunocytochemistry
Publisher:	John Wiley & Sons
ISSN:	0022-3417
Last Modified:	17 Oct 2022 10:00
URI:	https://orca.cardiff.ac.uk/id/eprint/6522

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