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at serine 118 in primary breast cancer and in tamoxifen-resistant tumours is indicative of a complex role for ER phosphorylation in breast cancer progression
1 Departments of Oncology,
2 Histopathology,
3 Surgery and
4 Social Science and Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK
5 Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff University, Cardiff, UK
6 Department of Tumor Endocrinology, Institute of Cancer Biology, Danish Cancer Society, DK-2100, Copenhagen Ø, Denmark
(Requests for offprints should be addressed to S Ali; Email: simak.ali{at}imperial.ac.uk)
Oestrogen receptor-
(ER) is an important prognostic marker in breast cancer and endocrine therapies are designed to inhibit or prevent ER activity. In vitro studies have indicated that phosphorylation of ER, in particular on serine 118 (S118), can result in activation in a ligand-independent manner, thereby potentially contributing to resistance to endocrine agents, such as tamoxifen and aromatase inhibitors. Here we report the immunohistochemistry (IHC) of S118 phosphorylation in 301 primary breast tumour biopsies. Surprisingly, this analysis shows that S118 phosphorylation is higher in more differentiated tumours, suggesting that phosphorylation at this site is associated with a good prognosis in patients not previously treated with endocrine agents. However, we also report that S118 phosphorylation was elevated in tumour biopsies taken from patients who had relapsed following tamoxifen treatment, when compared to pre-treatment biopsies. Taken together, these data are consistent with the view that S118 phosphorylation is a feature of normal ER function and that increases in levels of phosphorylation at this site may play a key role in the emergence of endocrine resistance in breast cancer.
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