title: Surgical intervention for symptomatic benign prostatic hyperplasia is correlated with expression of the AP-1 transcription factor network.
abstract: BACKGROUND
  Approximately one-third of patients fail medical treatment for benign prostatic hyperplasia and associated lower urinary tract symptoms (BPH/LUTS) requiring surgical intervention. Our purpose was to establish a molecular characterization for patients undergoing surgical intervention for LUTS to address therapeutic deficiencies.
  
  
  METHODS
  Clinical, molecular, and histopathological profiles were analyzed in 26 patients undergoing surgery for severe LUTS. Incidental transitional zone nodules were isolated from 37 patients with mild symptoms undergoing radical prostatectomy. Clinical parameters including age, prostate volume, medication, prostate specific antigen, symptom score, body mass index, and incidence of diabetes were collected. Multivariate logistic regression analysis with adjustments for potential confounding variables was used to examine associations between patient clinical characteristics and molecular targets identified through molecular profiling.
  
  
  RESULTS
  Compared to incidental BPH, progressive symptomatic BPH was associated with increased expression of the activating protein-1 transcription factor/chemokine network. As expected, inverse correlations were drawn between androgen receptor levels and age, as well as between 5α-reductase inhibitor (5ARI) treatment and tissue prostate specific antigen levels; however, a novel association was also drawn between 5ARI treatment and increased c-FOS expression.
  
  
  CONCLUSIONS
  This study provides molecular evidence that a network of pro-inflammatory activating protein-1 transcription factors and associated chemokines are highly enriched in symptomatic prostate disease, a profile that molecularly categorizes with many other chronic autoimmune diseases. Because 5ARI treatment was associated with increased c-FOS expression, future studies should explore whether increased activating protein-1 proteins are causal factors in the development of symptomatic prostate disease, inflammation or resistance to traditional hormonal therapy.
authors: Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors: Opal
authors: O
authors: Lin-Tsai
authors: Peter E
authors: PE
authors: Clark
authors: Nicole L
authors: NL
authors: Miller
authors: Jay H
authors: JH
authors: Fowke
authors: Omar
authors: O
authors: Hameed
authors: Simon W
authors: SW
authors: Hayward
authors: Douglas W
authors: DW
authors: Strand
mesh_terms: D000368:Aged; D006801:Humans; D059411:Lower Urinary Tract Symptoms / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000378:metabolism* / Q000601:surgery; D011470:Prostatic Hyperplasia / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D018808:Transcription Factor AP-1
keywords: AP-1 transcription factors; American Urological Association Symptom Score; benign prostatic hyperplasia; inflammation; lower urinary tract symptoms