Cheng, K. K.W., Dickson, A., Gujam, F. J.A., McMillan, D. C. and Edwards, J. (2017) The relationship between oestrogen receptor-alpha phosphorylation and the tumour microenvironment in patients with primary operable ductal breast cancer. Histopathology, 70(5), pp. 782-797. (doi: 10.1111/his.13134) (PMID:27891654)
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Abstract
Aims: Although the role of phosphorylation of oestrogen receptor (ER) at serines 118 (p-S118) and 167 (p-S167) has been studied, the relationship between p-S118, p-S167 and the tumour microenvironment in ER-positive primary operable ductal breast cancers have not been investigated. The aims of this study are to investigate (i) the relationship between p-S118/p-S167 and the tumour microenvironment, and (ii) the effect of p-S118/167 on survival and recurrence in ER-positive primary operable ductal breast cancers. Methods and results: Patients presenting at three Glasgow hospitals between 1995 and 1998 with invasive ductal ER-positive primary breast cancers were studied (n = 294). Immunohistochemical staining of p-S118 and p-S167 was performed and their association with clinicopathological characteristics, cancer-specific survival (CSS) and recurrence-free interval (RFI) were examined. In the whole cohort, tumour size (P < 0.05) and microvessel density (P < 0.05) were associated with high p-S118 while increased micovessel density (P < 0.05), apoptosis (P < 0.05), general inflammatory infiltrate measured using the Klintrup–Makinen score (P < 0.05) and macrophage infiltrate (P < 0.05) were found to be associated with high p-S167. Only high p-S167 was associated with shorter CSS (P < 0.005) and shorter RFI in the whole cohort (P = 0.001) and separately in the luminal A (P < 0.05) and B tumours (P < 0.05). Conclusions: This study showed that both p-S118 and p-S167 were associated with several microenvironmental factors, including increased microvessel density. In particular, p-S167 was associated with reduced RFI and CSS in the whole cohort and RFI in luminal A and B tumours and could possibly be employed to predict response to kinase inhibitors.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Dickson, Ms Ashley and Edwards, Professor Joanne and Gujam, Mrs Fadia and McMillan, Professor Donald |
| Authors: | Cheng, K. K.W., Dickson, A., Gujam, F. J.A., McMillan, D. C., and Edwards, J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing |
| Journal Name: | Histopathology |
| Publisher: | Wiley |
| ISSN: | 0309-0167 |
| ISSN (Online): | 1365-2559 |
| Published Online: | 28 November 2016 |
| Copyright Holders: | Copyright © 2016 John Wiley & Sons Ltd. |
| First Published: | First published in Histopathology 70(5):782-797 |
| Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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