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p14ARF stabilises nuclear p53, with a variable expression of p14ARF mRNA in breast cancers. In vitro, nuclear p14ARF binds Hdm2 to block Hdm2-dependent nucleocytoplasmic shuttling of p53, which is required before cytoplasmic degradation of p53. p14ARF is negatively regulated by p53 and through p53-independent pathways. No studies have yet examined levels of p14ARF protein expression in breast cancer and their relationship to Hdm2/p53 immunoreactivity or subcellular localisation. Previously, immunohistochemical expression of cytoplasmic p14ARF, p53 and Hdm2 has been described. HER-2 (c-erbB2/neu) predicts prognosis and interacts with the p14ARF/Hdm2 pathway to inactivate p14ARF and to influence Hdm2 activity and localisation. This study examined p14ARF and p53/Hdm2 expression and subcellular localisation by using immunohistochemistry in a series of invasive ductal breast cancers (IDCs) with concomitant ductal carcinoma in situ (DCIS), to evaluate whether findings in vitro were related to clinicopathological parameters such as HER-2 and their effect on patient outcome.

p14ARF expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and Hdm2