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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]

Abstract: Most cancers comprise a heterogenous population of cells with marked differences in their potential to proliferate as well as the ability to reconstitute the tumor upon transplantation. Cancer stem cells are a minor population of tumor cells that possess the stem cell property of self-renewal. Dysregulation of stem cell self-renewal is a likely requirement for the development of cancer. Cell signaling pathways shared by stem cells and cancer cells lend further evidence for a possible link between these 2 populations of cells. Study of the differentiation pathways of normal and abnormal prostate growth has led to the development of a stem cell model for prostate cancer. The basal layer of the normal prostate is believed to be populated by prostate epithelial stem cells and a population of transit-amplifying cells intermediate in differentiation to the stem and fully differentiated cells. There is recent evidence suggesting that prostate cancer occurs from malignant transformation of stem/progenitor cells, thereby resisting apoptosis and spawning proliferation. This new model for prostate cancer will have significant ramifications for the way this disease is studied and treated. Furthermore, through targeting the prostate cancer stem cell and its dysregulated self-renewal, therapies for treatment of prostate cancer are likely to improve. [Copyright &y& Elsevier]