1. Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score.
- Author
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Lam, John S., Seligson, David B., Hong Yu, Ali Li, Eeva, Mervi, Pantuck, Allan J., Gang Zeng, Horvath, Steve, and Belldegrun, Arie S.
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ENDONUCLEASES , *GENE expression , *PROSTATE cancer , *DNA microarrays , *CANCER cells , *IMMUNOHISTOCHEMISTRY - 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. 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. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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