title: Tumour Cannabinoid CB(1) receptor and phosphorylated epidermal growth factor receptor expression are additive prognostic markers for prostate cancer.
abstract: BACKGROUND
  In cultured prostate cancer cells, down-regulation of epidermal growth factor receptor (EGFR) has been implicated in mediating the antiproliferative effect of the endogenous cannabinoid (CB) ligand anandamide. Using a well-characterised cohort of prostate cancer patients, we have previously reported that expression levels of phosphorylated EGFR (pEGFR-IR) and CB(1) receptor (CB(1)IR) in tumour tissue at diagnosis are markers of disease-specific survival, but it is not known whether the two markers interact in terms of their influence on disease severity at diagnosis and disease outcome.
  
  
  RESULTS
  Data from a cohort of 419 patients who were diagnosed with prostate cancer at transurethral resection for voiding difficulties was used. Scores for both tumour CB(1)IR and pEGFR-IR were available in the database. Of these, 235 had been followed by expectancy until the appearance of metastases. For patients scored for both parameters, Cox proportional-hazards regression analyses using optimal cut-off scores indicated that the two measures provided additional diagnostic information not only to each other, but to that provided by the tumour stage and the Gleason score. When the cases were divided into subgroups on the basis of these cut-off scores, the patients with both CB(1)IR and pEGFR-IR scores above their cut-off had a poorer disease-specific survival and showed a more severe pathology at diagnosis than patients with high pEGFR-IR scores but with CB(1)IR scores below the cut-off.
  
  
  CONCLUSIONS
  These data indicate that a high tumour CB(1) receptor expression at diagnosis augments the deleterious effects of a high pEGFR expression upon disease-specific survival.
authors.affiliation: Department of Pharmacology and Clinical Neuroscience, Pharmacology, Umeå University, Umeå, Sweden.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Fowler
authors.forename: Peter
authors.initials: P
authors.lastname: Hammarsten
authors.forename: Anders
authors.initials: A
authors.lastname: Bergh
mesh_terms: D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000378:metabolism*; D012372:ROC Curve; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D012044:Regression Analysis
chemical_list: D043884:Receptor, Cannabinoid, CB1; D066246:ErbB Receptors