title: Histopathological changes associated with high intensity focused ultrasound (HIFU) treatment for localised adenocarcinoma of the prostate.
abstract: OBJECTIVE
  Investigation of the histopathological changes in prostatectomy specimens of patients with prostate cancer after high intensity focused ultrasound (HIFU) and identification of immunohistochemical markers for tissue damage after HIFU treatment.
  
  
  METHODS
  Nine patients diagnosed with adenocarcinoma of the prostate underwent unilateral HIFU treatment seven to 12 days before radical prostatectomy. The prostatectomy specimens were analysed histologically. Immunohistochemical staining and electron microscopy were performed to characterise more subtle phenotypic changes.
  
  
  RESULTS
  All prostatectomy specimens revealed well circumscribed HIFU lesions at the dorsal side of the prostate lobe treated. Most epithelial glands in the centre of the HIFU lesions revealed signs of necrosis. Glands without apparently necrotic features were also situated in the HIFU lesions, raising the question of whether lethal destruction had occurred. This epithelium reacted with antibodies to pancytokeratin, prostate specific antigen (PSA), and Ki67, but did not express cytokeratin 8, which is indicative of severe cellular damage. Ultrastructural examination revealed disintegration of cellular membranes and cytoplasmic organelles consistent with cell necrosis. HIFU treatment was incomplete at the ventral, lateral, and dorsal sides of the prostate lobe treated.
  
  
  CONCLUSIONS
  HIFU treatment induces a spectrum of morphological changes ranging from apparent light microscopic necrosis to more subtle ultrastructural cell damage. All HIFU lesions are marked by loss of cytokeratin 8. HIFU does not affect the whole area treated, leaving vital tissue at the ventral, lateral, and dorsal sides of the prostate.
authors.affiliation: Department of Pathology, University Hospital Nijmegen, The Netherlands. G.vanleenders@pathol.azn.nl
authors.forename: G J
authors.initials: GJ
authors.lastname: Van Leenders
authors.forename: H P
authors.initials: HP
authors.lastname: Beerlage
authors.forename: E T
authors.initials: ET
authors.lastname: Ruijter
authors.forename: J J
authors.initials: JJ
authors.lastname: de la Rosette
authors.forename: C A
authors.initials: CA
authors.lastname: van de Kaa
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000628:therapy* / Q000648:ultrastructure; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D006801:Humans; D007633:Keratins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009363:Neoplasm Proteins / Q000378:metabolism; D011467:Prostate / Q000473:pathology; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000628:therapy* / Q000648:ultrastructure; D014464:Ultrasonic Therapy
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D007633:Keratins