title: The presence of carboxypeptidase-M in tumour cells signifies epidermal growth factor receptor expression in lung adenocarcinomas: the coexistence predicts a poor prognosis regardless of EGFR levels.
abstract: OBJECTIVE
  Carboxypeptidase-M (CPM) is a membrane-bound peptidase that metabolizes peptides, and is present in pneumocytes. CPM hydrolyses the C-terminal arginine of epidermal growth factor (EGF) resulting in des-Arg53-EGF which binds to the EGF receptor (EGFR) with an equal or greater affinity than native EGF. Therefore, this study focused on the possible presence of CPM in human lung adenocarcinomas (ADC) and evaluated the relationship between CPM and EGFR by assessing the impact of expressions on patient clinical outcome.
  
  
  METHODS
  This is a retrospective study of 110 patients who underwent resection of the primary tumour (92) or metastatic tissues (18) for treatment or diagnosis. Immunohistochemistry (IHC) for CPM and EGFR was made in serial sections using standard methods.
  
  
  RESULTS
  This study demonstrates for the first time that 23.6% of ADCs express carboxypeptidase-M (26/110), mainly in membrane-bound forms. The amounts and the extent of CPM within tumours vary from low levels to obviously overexpressed forms. The immunohistochemical positivity (+) for CPM in ADCs negatively correlated with disease survival. In addition, 80% of CPM+ adenocarcinomas (21/26) showed a coexpression with EGFR suggesting a high prevalence for coexistence. The follow up data indicated a significantly shorter 5-year survival time for patients with CPM+-EGFR+ (double-positive) tumours compared to those harbouring neoplasias negative for both proteins (9.5 vs. 60.4% survivals, P < 0.001).
  
  
  CONCLUSIONS
  The fact that CPM+ ADCs often co-express with EGFR suggests a functional-regulatory link between these proteins which might have therapeutical consequences. The present novel data could lead to improved IHC tests in lung adenocarcinomas for EGFR expression.
authors.affiliation: Department of Pathology, University of Debrecen, Medical and Health Science Center, Nagyerdei krt. 98, 4032, Debrecen, Hungary.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Tsakiris
authors.forename: Gyorgyike
authors.initials: G
authors.lastname: Soos
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Nemes
authors.forename: Sandor Sz
authors.initials: SS
authors.lastname: Kiss
authors.forename: Csilla
authors.initials: C
authors.lastname: Andras
authors.forename: Janos
authors.initials: J
authors.lastname: Szantó
authors.forename: Balazs
authors.initials: B
authors.lastname: Dezso
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D066246:ErbB Receptors / Q000032:analysis*; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D008297:Male; D008666:Metalloendopeptidases / Q000032:analysis*; D009367:Neoplasm Staging; D012189:Retrospective Studies
chemical_list: D058851:GPI-Linked Proteins; D066246:ErbB Receptors; C058479:carboxypeptidase M; D008666:Metalloendopeptidases