title: Clinicopathological and prognostic significance of mitogen-activated protein kinases (MAPK) in breast cancers.
abstract: BACKGROUND
  Mitogen-activated protein kinases (MAPKs) are signalling transduction molecules that have different functions and diverse behaviour in cancer. In breast cancer, MAPK is related to oestrogen receptor (ER) and HER2.
  
  
  METHODS
  Protein expression of a large panel of MAPKs (JNK1/2, ERK, p38, C-JUN and ATF2 including phosphorylated forms) were assessed immunohistochemically in a large (n = 1400) and well-characterised breast cancer series prepared as tissue microarray. Moreover, reverse phase protein array was applied to quantify protein expression of MAPKs in six breast cancer cell lines with different phenotypes including HER2-transfected cells.
  
  
  RESULTS
  MAPKs expression was associated with clinicopathological variables characteristic of good prognosis. These associations were most significant in the whole series and in the ER+ subgroup compared to other BC classes. Most of MAPKs showed a positive association with ER, BCL2 and better outcome and were negatively associated with the proliferation marker Ki67 and p53. Association of MAPK with HER2 was mainly seen in the ER- subgroup. Reverse phase protein array confirmed immunohistochemistry results and revealed differential expression of MAPK proteins in ER+ and ER- cell lines.
  
  
  CONCLUSIONS
  MAPKs are associated with good prognosis and their expression is mainly related to ER. Studying a large panel rather than individual biomarkers may provide improved understanding of the pathway.
authors: Division of Cancer and Stem Cells, Department of Histopathology, School of Medicine, Nottingham City Hospital, The University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UK.|Department of Pathology, Mosul Medical School, University of Mosul, Mosul, Iraq.
authors: Dena A J
authors: DA
authors: Ahmad
authors: School of Medicine, Queen's Medical Hospital, University of Nottingham, Derby Road, Nottingham, NG7 2UH, UK. ola.negm@nottingham.ac.uk.|Faculty of Medicine, Medical Microbiology and Immunology Department, Mansoura University, Mansoura, Egypt. ola.negm@nottingham.ac.uk.
authors: Ola H
authors: OH
authors: Negm
authors: Academic Unit of Clinical Oncology, School of Medicine, Nottingham City Hospital, University of Nottingham, Nottingham, UK.
authors: M Layth
authors: ML
authors: Alabdullah
authors: Department of Genetics, Cell Biology and Anatomy, University of Nebraska, Omaha, USA.
authors: Sameer
authors: S
authors: Mirza
authors: School of Medicine, Queen's Medical Hospital, University of Nottingham, Derby Road, Nottingham, NG7 2UH, UK.|Faculty of Medicine, Medical Microbiology and Immunology Department, Mansoura University, Mansoura, Egypt.
authors: Mohamed R
authors: MR
authors: Hamed
authors: Department of Genetics, Cell Biology and Anatomy, University of Nebraska, Omaha, USA.
authors: Vimla
authors: V
authors: Band
authors: Division of Cancer and Stem Cells, Department of Histopathology, School of Medicine, Nottingham City Hospital, The University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors: Andrew R
authors: AR
authors: Green
authors: Division of Cancer and Stem Cells, Department of Histopathology, School of Medicine, Nottingham City Hospital, The University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors: Ian O
authors: IO
authors: Ellis
authors: Division of Cancer and Stem Cells, Department of Histopathology, School of Medicine, Nottingham City Hospital, The University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors: Emad A
authors: EA
authors: Rakha
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D040901:Proteomics / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D020928:Mitogen-Activated Protein Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human
keywords: Breast cancer; MAPK signalling pathways; Reverse phase protein microarray (RPPA)