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Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score
Author(s) -
LAM JOHN S.,
SELIGSON DAVID B.,
YU HONG,
LI AI,
EEVA MERVI,
PANTUCK ALLAN J.,
ZENG GANG,
HORVATH STEVE,
BELLDEGRUN ARIE S.
Publication year - 2006
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2006.06224.x
Subject(s) - prostate cancer , endonuclease , medicine , prostate , cancer , oncology , urology , cancer research , biology , gene , genetics
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 ≥ 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 ≥ 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.