title: Morphological transition of proliferative inflammatory atrophy to high-grade intraepithelial neoplasia and cancer in human prostate.
abstract: BACKGROUND
  Inflammation has been implicated as a potential etiological agent in human prostate cancer (PCa). Proliferative inflammatory atrophy (PIA) in prostate consists of areas of glandular atrophy associated with chronic inflammation and epithelial cell proliferation. It has been suggested that PIA is a candidate precursor of prostate malignancy. We aimed to explore the morphological transition between PIA and co-existing high-grade prostate intraepithelial neoplasia (HGPIN) and/or PCa.
  
  
  METHODS
  Serial slides of 50 whole-mounted radical prostatectomies were studied with H&E staining and immunostaining of cytokeratin 5 (CK5), glutathione S-transferase pi (GSTP1), hepatocyte growth factor receptor (c-MET), CCAAT/enhancer binding protein beta (C/EBPbeta), and Ki-67. Utilizing immunohistochemical stains to examine HGPIN, PIA-merging HGPIN, and PIA-merging PCa lesions, respectively.
  
  
  RESULTS
  A total of 1,188 HGPIN lesions were identified, of which 17% (198) were in the morphological process of merging with PIA. Thirty-six PIA-merging PCa lesions were also detected. The atrophic epithelial cells in such merging lesions had increased Ki-67 index and an intermediate phenotype: increased expression for CK5, GSTP1, c-MET, and C/EBPbeta. In addition, clusters of atypical epithelial cell hyperplasia, that is, with nuclear enlargement, hyperchromasia, and prominent nucleoli, were found in 16 PIA lesions. Such clusters of atypical cells that meet the criteria for HGPIN still expressed CK5 and were adjacent to focal chronic inflammation.
  
  
  CONCLUSIONS
  Direct morphological transition between PIA and HGPIN and/or PCa was present. The atrophic cells in these merging lesions had an intermediate phenotype. Clusters of atypical epithelial cell hyperplasia might represent the earliest transition from PIA to HGPIN. Prostate 69: 1378-1386, 2009. (c) 2009 Wiley-Liss, Inc.
authors.affiliation: Department of Urology, Lundberg Laboratory for Cancer Research, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Wanzhong
authors.initials: W
authors.lastname: Wang
authors.forename: Anders
authors.initials: A
authors.lastname: Bergh
authors.forename: Jan-Erik
authors.initials: JE
authors.lastname: Damber
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology*; D001284:Atrophy; D002455:Cell Division / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000276:immunology / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D011230:Precancerous Conditions / Q000276:immunology / Q000473:pathology*; D011467:Prostate / Q000276:immunology / Q000473:pathology; D019048:Prostatic Intraepithelial Neoplasia / Q000276:immunology / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000473:pathology*; D011472:Prostatitis / Q000276:immunology / Q000473:pathology*
chemical_list: D019394:Ki-67 Antigen