Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score

BJU Int. 2006 Aug;98(2):445-51. doi: 10.1111/j.1464-410X.2006.06224.x.


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.

Materials and 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Biomarkers, Tumor / metabolism*
  • Cohort Studies
  • Flap Endonucleases / metabolism*
  • Humans
  • Immunohistochemistry
  • Male
  • Microarray Analysis
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / pathology


  • Biomarkers, Tumor
  • Flap Endonucleases
  • FEN1 protein, human
  • Prostate-Specific Antigen