title: Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score.
abstract: OBJECTIVE
  To investigate the expression and potential clinical usefulness of structure-specific flap endonuclease 1 (FEN-1) in human primary prostate cancer using tissue microarray technology, as FEN-1 was recently identified to be overexpressed in CL1.1, the most aggressive clone generated from the hormone-refractory prostate cancer cell line CL1.
  
  
  METHODS
  Immunohistochemistry was performed on tissue microarrays constructed from paraffin-embedded specimens of primary prostate cancer from 246 patients who had had a radical prostatectomy. Prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH) and normal prostate epithelium were represented on the array. FEN-1 nuclear expression was scored based on the percentage of target cells staining positively, and correlated with Gleason score, preoperative prostate-specific antigen (PSA) level and pathological stage. The time to PSA recurrence was also analysed.
  
  
  RESULTS
  The mean expression of FEN-1 was significantly higher in cancer (36.7%) than in normal (13.2%), BPH (4.5%) and PIN (15.4%) specimens (P < 0.001). FEN-1 expression was significantly correlated with Gleason score (ó = 0.23, P = 0.002). A higher preoperative serum PSA level (P = 0.015), Gleason score > or = 7 (P < 0.001), seminal vesicle invasion (P < 0.001) and capsular involvement (P = 0.004) were associated with PSA recurrence, whereas FEN-1 expression was not. In a multivariate analysis, only Gleason score > or = 7 (P < 0.001), seminal vesicle invasion (P = 0.005) and capsular involvement (P = 0.009) were retained as independent predictors for PSA recurrence.
  
  
  CONCLUSIONS
  FEN-1 is overexpressed in prostate cancer compared with matched normal prostate, and its expression increases with tumour dedifferentiation, as shown by increasing Gleason score. These results suggest that FEN-1 might be a potential marker for selecting patients at high risk, and a potential target for prostate cancer diagnosis and therapy.
authors.affiliation: Department of Urology, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA 90095-1738, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Lam
authors.forename: David B
authors.initials: DB
authors.lastname: Seligson
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Ai
authors.initials: A
authors.lastname: Li
authors.forename: Mervi
authors.initials: M
authors.lastname: Eeva
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Pantuck
authors.forename: Gang
authors.initials: G
authors.lastname: Zeng
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.forename: Arie S
authors.initials: AS
authors.lastname: Belldegrun
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015331:Cohort Studies; D045585:Flap Endonucleases / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D045585:Flap Endonucleases; C468317:FEN1 protein, human; D017430:Prostate-Specific Antigen