The relationship between oestrogen receptor-alpha phosphorylation and the tumour microenvironment in patients with primary operable ductal breast cancer

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:McMillan, Professor Donald and Dickson, Ms Ashley and Edwards, Professor Joanne and Gujam, Mrs Fadia
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 > Institute 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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
706591Relationship between IKK alpha (IKK??), Oestrogen Receptor alpha (ER??) phosphorylation and clinical outcome measures in ER positive breast cancer.Joanne EdwardsMedical Research Scotland (MED-SCOT)Vac-820-2015ICS - EXPERIMENTAL THERAPEUTICS