title: The relationship between oestrogen receptor-alpha phosphorylation and the tumour microenvironment in patients with primary operable ductal breast cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: School of Medicine, University of Glasgow, Glasgow, UK.
authors.forename: Kelvin K W
authors.identifier: http://orcid.org/0000-0001-5618-082X
authors.initials: KK
authors.lastname: Cheng
authors.affiliation: Unit of Experimental Therapeutics, Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Ashley
authors.initials: A
authors.lastname: Dickson
authors.affiliation: Academic Unit of Surgery, College of Medical, Veterinary and Life Sciences, University of Glasgow, Royal Infirmary, Glasgow, UK.
authors.forename: Fadia J A
authors.initials: FJ
authors.lastname: Gujam
authors.affiliation: Academic Unit of Surgery, College of Medical, Veterinary and Life Sciences, University of Glasgow, Royal Infirmary, Glasgow, UK.
authors.forename: Donald C
authors.initials: DC
authors.lastname: McMillan
authors.affiliation: Unit of Experimental Therapeutics, Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Edwards
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D010766:Phosphorylation; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment
chemical_list: D047628:Estrogen Receptor alpha
keywords: breast cancer; oestrogen receptor; prognosis; serine 118; serine 167; tumour microenvironment