title: ErbB2 receptor immunoreactivity in prostate cancer: relationship to the androgen receptor, disease severity at diagnosis and disease outcome.
abstract: BACKGROUND
  ErbB2 is a member of the epidermal growth factor family of tyrosine kinases that is centrally involved in the pathogenesis of prostate cancer and several studies have reported that a high expression of this protein has prognostic value. In the present study, we have investigated whether tumour ErbB2 immunoreactivity (ErbB2-IR) has clinically useful prognostic value, i.e. that it provides additional prognostic information to that provided by routine clinical tests (Gleason score, tumour stage).
  
  
  RESULTS
  ErbB2-IR was measured in a well-characterised tissue microarray of tumour and non-malignant samples obtained at diagnosis. Additionally, mRNA levels of ErbB2-IR in the prostate were determined in the rat following manipulation of circulating androgen levels. Tumour ErbB2-IR was significantly associated with the downstream signalling molecule phosphorylated-Akt and with the cell proliferation marker Ki-67. The significant association of tumour ErbB2-IR with the Gleason score at diagnosis was lost when controlled for the association of both parameters with Ki-67. In the rat prostate, mRNA for ErbB2 was inversely associated with circulating androgen levels. There was no association between ErbB2-IR and the androgen receptor (AR)-IR in the tumours, but an interaction between the two parameters was seen with respect to their association with the tumour stage. Tumour ErbB2-IR was confirmed to be a prognostic marker for disease-specific survival, but it did not provide significant additive information to the Gleason score or to Ki-67.
  
  
  CONCLUSIONS
  It is concluded that tumour ErbB2-IR is of limited clinical value as a prognostic marker to aid treatment decisions, but could be of pathophysiological importance in prostate cancer.
authors.affiliation: Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Hammarsten
authors.affiliation: Department of Pharmacology and Clinical Neuroscience, Pharmacology, Umeå University, Umeå, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Winther
authors.affiliation: Department of Surgical and Perioperative Sciences, Urology, Umeå University, Umeå, Sweden.
authors.forename: Stina H
authors.initials: SH
authors.lastname: Rudolfsson
authors.affiliation: Umeå School of Business and Economics, Department of Statistics, Umeå University, Umeå, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Häggström
authors.affiliation: Department of Integrative Medical Biology, Anatomy, Umeå University, Umeå, Sweden.
authors.forename: Amar
authors.initials: A
authors.lastname: Karalija
authors.affiliation: Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Egevad
authors.affiliation: Department of Urology, Central Hospital, Västerås, Sweden.
authors.forename: Torvald
authors.initials: T
authors.lastname: Granfors
authors.affiliation: Department of Pharmacology and Clinical Neuroscience, Pharmacology, Umeå University, Umeå, Sweden.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Fowler
mesh_terms: D000728:Androgens / Q000378:metabolism; D000818:Animals; D002369:Castration; D018450:Disease Progression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D012044:Regression Analysis; D015398:Signal Transduction; D046888:Tissue Array Analysis
chemical_list: D000728:Androgens; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen