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Overexpression of TFAP2C in invasive breast cancer correlates with a poorer response to anti‐hormone therapy and reduced patient survival
Author(s) -
Gee JMW,
Eloranta JJ,
Ibbitt JC,
Robertson JFR,
Ellis IO,
Williams T,
Nicholson RI,
Hurst HC
Publication year - 2009
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2430
Subject(s) - tamoxifen , breast cancer , immunohistochemistry , medicine , hormone therapy , oncology , biology , hormone , transcription factor , cancer research , endocrinology , cancer , gene , genetics
The AP‐2γ 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‐2α and AP‐2γ 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‐2γ. Heterogeneous, exclusively nuclear expression of AP‐2γ 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‐2γ 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‐2γ 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‐2γ, acquisition of resistance to this and other anti‐hormone measures (eg faslodex or oestrogen deprivation) is associated with high levels of nuclear AP‐2γ. Together these data suggest that elevated tumour AP‐2γ expression can contribute to the failure of cells to growth arrest following anti‐hormone treatment and lead to sustained growth and poorer patient outcome. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.