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The relationship between oestrogen receptor‐alpha phosphorylation and the tumour microenvironment in patients with primary operable ductal breast cancer
Author(s) -
Cheng Kelvin K W,
Dickson Ashley,
Gujam Fadia J A,
McMillan Donald C,
Edwards Joanne
Publication year - 2017
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13134
Subject(s) - immunohistochemistry , medicine , breast cancer , cancer , microvessel , tumor microenvironment , oncology , cohort , mammary gland , pathology
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.