title: Detection of the epidermal growth factor receptor, amphiregulin and epiregulin in formalin-fixed paraffin-embedded human placenta tissue by matrix-assisted laser desorption/ionization mass spectrometry imaging.
abstract: The study of the expression and the tissue distribution of the tyrosine kinase drug-target epidermal growth factor receptor (EGFR) is of interest in oncology as a marker of potential efficacy of treatment. It has been reported, however, that the response rates to anti-EGFR drugs are poorly linked to its expression. Clinical studies have also revealed a patient response correlation with the expression levels of two EGFR ligands; amphiregulin and epiregulin. Here, we report the development of a matrix-assisted laser desorption/ionisation mass spectrometry imaging methodology for the study of EGFR, epiregulin and amphiregulin distribution in formalin fixed paraffin embedded human placental tissue and a comparison to expression patterns obtained by immunohiostochemistry. Using on-tissue digests and imaging of specific peptides, the tissue distribution of these proteins has been obtained down to 30 microm spatial resolution.
authors.affiliation: School of Medicine, Al-Jouf University, Sakaka, Kingdom of Saudi Arabia. k.mahmoud@leeds.ac.uk
authors.forename: Khaled
authors.initials: K
authors.lastname: Mahmoud
authors.forename: Laura M
authors.initials: LM
authors.lastname: Cole
authors.forename: Jillian
authors.initials: J
authors.lastname: Newton
authors.forename: Sabah
authors.initials: S
authors.lastname: Mohamed
authors.forename: Maher
authors.initials: M
authors.lastname: Al-Enazi
authors.forename: Phil
authors.initials: P
authors.lastname: Quirke
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Clench
mesh_terms: D000595:Amino Acid Sequence; D066258:Amphiregulin; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor / Q000032:analysis* / Q000737:chemistry; D066260:Epiregulin; D066246:ErbB Receptors / Q000032:analysis* / Q000737:chemistry; D005260:Female; D005557:Formaldehyde; D006023:Glycoproteins / Q000032:analysis* / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis* / Q000737:chemistry; D057054:Molecular Imaging / Q000379:methods*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D016612:Paraffin Embedding; D010449:Peptide Mapping; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D016707:Tissue Fixation
chemical_list: C587848:AREG protein, human; D066258:Amphiregulin; D066255:EGF Family of Proteins; C587880:EREG protein, human; D066260:Epiregulin; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D005557:Formaldehyde; D004815:Epidermal Growth Factor; D066246:ErbB Receptors