title: Erythropoietin receptor is not a surrogate marker for tumor hypoxia and does not correlate with survival in head and neck squamous cell carcinomas.
abstract: OBJECTIVE
  To evaluate erythropoietin receptor (EPOR) expression in human head and neck squamous cell carcinomas and correlate this to the presence of tumor hypoxia and treatment outcome.
  
  
  METHODS
  Eighty-five patients with locally advanced tumors of the head and neck were included. Of these, 34 were given the hypoxia marker pimonidazole i.v. 2 h prior to biopsy taking. Contiguous paraffin embedded biopsies were stained for EPOR expression and, if administered, for pimonidazole binding. Immunohistochemical staining for EPOR was interpreted semiquantitatively according to a composite scale, ranging from 0 to 200. Pimonidazole positivity was quantitatively analyzed in a semiautomatic way.
  
  
  RESULTS
  Diffuse weak-to-moderate cytoplasmic and membrane EPOR immunostaining was observed in 80 of 85 biopsies (94%) and staining scores ranged from 0 to 198 (median 100). No correlations were found between EPOR expression, and the primary tumor site, T-stage or N-stage. Also, There was no association between EPOR expression and treatment outcome. The degree of tumor hypoxia represented by the relative area of pimonidazole binding varied between 0 and 26% (median 7%). Contiguous biopsy sections showed a lack of colocalization between EPOR and pimonidazole binding.
  
  
  CONCLUSIONS
  EPOR expression was demonstrated in the majority of the head and neck tumors. No colocalization was found between EPOR expression and pimonidazole binding indicating that the presence or absence of hypoxia did not necessarily indicate a distinct pattern of EPOR expression. The level of EPOR expression was not of prognostic significance in patients with head and neck cancer, although small effects of EPOR cannot be excluded because of the sample size of this study.
authors.affiliation: Department of Radiation Oncology, Radboud University Nijmegen Medical Center, The Netherlands. i.hoogsteen@rther.umcn.nl
authors.forename: Ilse J
authors.initials: IJ
authors.lastname: Hoogsteen
authors.forename: Wenny J M
authors.initials: WJ
authors.lastname: Peeters
authors.forename: Henri A M
authors.initials: HA
authors.lastname: Marres
authors.forename: Paul F J W
authors.initials: PF
authors.lastname: Rijken
authors.forename: Franciscus J A
authors.initials: FJ
authors.lastname: van den Hoogen
authors.forename: Albert J
authors.initials: AJ
authors.lastname: van der Kogel
authors.forename: Johannes H A M
authors.initials: JH
authors.lastname: Kaanders
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009593:Nitroimidazoles / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D009593:Nitroimidazoles; D017467:Receptors, Erythropoietin; C033815:pimonidazole