title: Prostate Biopsy Markers of Inflammation are Associated with Risk of Clinical Progression of Benign Prostatic Hyperplasia: Findings from the MTOPS Study.
abstract: OBJECTIVE
  Factors associated with worsening of benign prostatic hyperplasia are not well understood. We measured inflammatory markers from prostate biopsies to study if inflammation is related to clinical progression of benign prostatic hyperplasia.
  
  
  METHODS
  We measured inflammatory cell markers CD45, CD4, CD8 and CD68 in transition zone biopsies from 859 men in the MTOPS biopsy substudy. Using novel imaging techniques we quantified amounts of moderate/severe inflammation. Benign prostatic hyperplasia clinical progression was defined as a confirmed 4-point or greater increase in the AUA symptom score from baseline, or the occurrence of urinary incontinence or acute urinary retention. Baseline clinical parameters including concomitant medication use were determined. Kaplan-Meier curves and multivariate Cox proportional hazard models were used to determine the risk of progression.
  
  
  RESULTS
  Inflammation as measured by CD45, CD4 and CD68 increased the risk of clinical progression of benign prostatic hyperplasia. CD4 showed the highest risk where men in the highest tertile of moderate/severe inflammation were at twice the risk of progression compared to men in the lower 2 tertiles combined (HR 2.03, p=0.001). Inflammation was more strongly associated with progression defined by acute urinary retention or incontinence (HR ranging from 2.39 [CD8, p=0.03] to 3.08 [CD4, p=0.01]) than an AUA symptom score increase (CD4, HR 1.86, p=0.01). Men who reported use of nonsteroidal anti-inflammatory drugs or steroids at baseline tended to be at higher risk for progression.
  
  
  CONCLUSIONS
  Although our data show that inflammation increases the risk of progression, our findings suggest that inflammation has a greater role in men who have conditions requiring anti-inflammatory medications.
authors.affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. Electronic address: kathleen.torkko@ucdenver.edu.
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Torkko
authors.affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: R Storey
authors.initials: RS
authors.lastname: Wilson
authors.affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Smith
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: John W
authors.initials: JW
authors.lastname: Kusek
authors.affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Adrie
authors.initials: A
authors.lastname: van Bokhoven
authors.affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: M Scott
authors.initials: MS
authors.lastname: Lucia
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D001706:Biopsy; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D008396:Maryland / Q000453:epidemiology; D008875:Middle Aged; D011379:Prognosis; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D015704:CD4 Antigens; D016827:CD8 Antigens; D017493:Leukocyte Common Antigens; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: anti-inflammatory agents; disease progression; inflammation; prostatic hyperplasia