title: ERK1/2 is related to oestrogen receptor and predicts outcome in hormone-treated breast cancer.
abstract: The extracellular-regulated kinase (ERK) 1/2 is one of the members of the mitogen-activated protein kinases (MAPKs). MAPKs are transduction proteins that play a role in controlling diverse cellular functions including proliferation and survival. In breast cancer (BC), MAPKs are involved in oestrogen receptor (ER) and HER2 pathways. This study aims to assess the biological and clinical significance of ERK1/2 protein expression in BC. Immunohistochemistry was used to assess the expression of both total (ERK1/2) and phospholyated (p ERK1/2) ERK1/2 proteins in a large and well-characterised series of early stage BC (n = 1300) using tissue microarray technology. ERK1/2 expression was cytoplasmic, while p-ERK1/2 was observed in the nucleus (N-p-ERK1/2) and/or cytoplasm (C-p-ERK1/2). Both ERK1/2 and p-ERK1/2 were positiviely associated with markers of good prognosis including smaller size, lower grade, expression of hormone receptor and ER-related proteins and negatively associated with HER2, HER4, KI67 and p53. Outcome analysis showed an association between N-p-ERK1/2 and better outcome. In tamoxifen-treated cases, ERK1/2 expression was an independent prognostic marker of longer survival. ERK1/2 and p-ERK1/2 were associated with good prognosis. Importantly, positivity of ERK1/2 is independently associated with better outcome in tamoxifen-treated cases.
authors.affiliation: Department of Histopathology and Divison of Cancer and Stem Cells, School of Medicine, The University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham City Hospital, Nottingham, UK, denaakramj@yahoo.co.uk.
authors.forename: Dena A
authors.initials: DA
authors.lastname: Jerjees
authors.forename: M
authors.initials: M
authors.lastname: Alabdullah
authors.forename: Methaq
authors.initials: M
authors.lastname: Alkaabi
authors.forename: Rezvan
authors.initials: R
authors.lastname: Abduljabbar
authors.forename: Abir
authors.initials: A
authors.lastname: Muftah
authors.forename: Chris
authors.initials: C
authors.lastname: Nolan
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Green
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.forename: Emad A
authors.initials: EA
authors.lastname: Rakha
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D010766:Phosphorylation; D011379:Prognosis; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use; D046888:Tissue Array Analysis
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D013629:Tamoxifen; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3