Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score.
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.
Lam
John S
JS
Department of Urology, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA 90095-1738, USA.
Seligson
David B
DB
Yu
Hong
H
Li
Ai
A
Eeva
Mervi
M
Pantuck
Allan J
AJ
Zeng
Gang
G
Horvath
Steve
S
Belldegrun
Arie S
AS
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
D014408:Biomarkers, Tumor; D045585:Flap Endonucleases; C468317:FEN1 protein, human; D017430:Prostate-Specific Antigen