title: Possible Role of HER-2 in the Progression of Prostate Cancer from Primary Tumor to Androgen Independence.
abstract: BACKGROUND
  The expression of HER-2 in prostate cancer has been linked to disease progression. We analysed the presence of HER-2 expression in primary tumors in men undergoing radical prostatectomy, its association with clinical and pathological findings, and its expression in secondary circulating prostate cells (CPCs) during follow up, as well as links with biochemical failure and the effects of androgen blockade.
  
  
  METHODS
  Consecutive men undergoing radical prostatectomy for histologically confirmed prostate cancer were analyzed. HER-2 expression in the primary tumor was assessed using the HercepTest®, CPCs were identified from blood samples using standard immunocytochemistry with anti-PSA and positive samples with the HercepTest® to determine HER-2 expression. The influence of HER-2 expression on the frequency of biochemical failure and effects of androgen blockade was determined.
  
  
  RESULTS
  144 men with a mean age of 64.8±10.3 years participated, with a median follow up of 8.2 years. HER-2 was expressed in 20.8% of primary tumors; it was associated with vascular infiltration and older age, but not with other clinical pathological findings. Some 40.3% of men had secondary CPCs detected, of which 38% expressed HER-2. Men CPC (+) had a higher frequency of biochemical failure, but there was no difference in HER-2 expression of CPCs with the frequency of biochemical failure. After androgen blockade, men with HER-2 (+) positive secondary CPCs had a higher frequency of disease progression to castrate resistant disease.
  
  
  CONCLUSIONS
  HER-2 plays a dual role in the progression of prostate cancer; firstly it may increase the potential of tumor cells to disseminate from the primary tumor via the blood by increasing vascular infiltration. In the presence of androgens, there is no survival advantage of expressing HER-2, but once biochemical failure has occurred and androgen blockade started, HER-2 positive cells are resistant to treatment, survive and grow leading to castration resistant disease.
authors.affiliation: Hematology, Medicine, Hospital de Carabineros de Chile, Faculty of Medicine University Finis Terrae, Santiago, Chile E-mail : nigelpetermurray@gmail.com.
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Murray
authors.forename: Eduardo
authors.initials: E
authors.lastname: Reyes
authors.forename: Cynthia
authors.initials: C
authors.lastname: Fuentealba
authors.forename: Omar
authors.initials: O
authors.lastname: Jacob
authors.forename: Nelson
authors.initials: N
authors.lastname: Orellana
mesh_terms: D000367:Age Factors; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001808:Blood Vessels / Q000473:pathology; D018450:Disease Progression; D005485:Flutamide / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009360:Neoplastic Cells, Circulating / Q000737:chemistry / Q000378:metabolism*; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000378:metabolism*
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D005485:Flutamide; D017430:Prostate-Specific Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human