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Utility of tissue microarrays for profiling prognostic biomarkers in clinically localized prostate cancer： the expression of BCL-2, E-cadherin, Ki-67 and p53 as predictors of biochemical failure after radical prostatectomy with nested control for clinical and pathological risk factors

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Asian Journal of Andrology 2009年第1期11卷 109-118页

作者： Joseph Nariculam Alex Freeman simon bott Phillipa Munson Noriko Cable Nicola Brookman-Amissah Magali Williamson Roger S. Kirby John Masters Mark Feneley Institute of Urology Prostate Cancer Research Centre London W1 W 7E J UK Histopathology Diagnostics Statistics University College London London W1 W 7ET UK Prostate Cancer Research Centre London W1 G 8GT UK

A cure cannot be assured for all men with clinically localized prostate cancer undergoing radical treatment. Molecular markers would be invaluable if they could improve the prediction of occult metastatic disease. This study was carried out to investigate the expression of BCL-2, Ki-67, p53 and E-cadherin in radical prostatectomy specimens. We sought to assess their ability to predict early biochemical relapse in a specific therapeutic setting. Eighty-two patients comprising 41 case pairs were matched for pathological stage, Gleason grade and preoperative prostate-specific antigen （PSA） concentration. One patient in each pair had biochemical recurrence （defined as PSA ≥ 0.2 ng mL^-1 within 2 years of surgery） and the other remained biochemically free of disease （defined as undetectable PSA at least 3 years after surgery）. Immunohistochemical analysis was performed to assess marker expression on four replicate tissue microarrays constructed with benign and malignant tissue from each radical prostatectomy specimen. Ki-67, p53 and BCL-2, but not E-cadherin, were significantly upregulated in prostate adenocarcinoma compared with benign prostate tissue （P 〈 0.01）. However, no significant differences in expression of any of the markers were observed when comparing patients who developed early biochemical relapse with patients who had no biochemical recurrence. This study showed that expression of p53, BCL-2 and Ki-67 was upregulated in clinically localized prostate cancer compared with benign prostate tissue, with no alteration in E-cadherin expression. Biomarker upregulation had no prognostic value for biochemical recurrence after radical prostatectomy, even after considering pathological stage, whole tumour Gleason grade and preoperative serum PSA level.

关键词： immunohistochemistry prostate cancer prostatectomy

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Correlation of Urinary Engrailed-2 Levels to Tumour Volume and Pathological Stage in Men Undergoing Radical Prostatectomy

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Journal of Cancer Therapy 2013年第3期4卷 726-733页

作者： Hardev Pandha Saqib Javed Prasanna Sooriakumaran simon bott Bruce Montgomery Anthony Hutton Christopher Eden Christopher Eden Stephen E. Langley Richard Morgan Frimley Park Hospital NHS Foundation Trust Portsmouth Road Frimley UK Oncology Faculty of Health and Medical Sciences University of Surrey Guildford UK Royal Surrey County Hospital Guildford UK St. Georges Hospital London UK

The aim of this study was to assess the relationship between pre-prostatectomy urinary Engrailed-2 (EN2), a transcription factor secreted by prostate cancer cells, with tumour volume and pathological characteristics in resected prostate specimens. First pass urine samples (10 ml) without prior prostatic massage were collected and stored at –80°C. EN2 levels were measured using an enzyme-linked immunoabsorbent assay. Tumour volume in the prostatectomy specimens was determined histologically. 57 men undergoing RP in one urological cancer network were evaluated. EN2 was detected in 85% of RP patients. EN2 correlated with tumour volume (but not total prostatic volume) in a linear regression analysis, with increasing pathological T stage and margin positivity. Using three “cutoff levels” of tumour volume (0.5 ml, 1.3 ml and 2.5 ml) to define “significant disease”, men with “significant disease” had markedly higher levels of urinary EN2 (p Levels of urinary EN2 may be useful in predicting tumour volume in men with prostate cancer by potentially identifying men with small volume “insignificant” disease. This study justifies a larger multicentre evaluation of urinary EN2 levels as a biomarker of PC significance using cancer volume, pathological and PSA criteria.

关键词： Biomarker Prostate Cancer Urine

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