Original Article
Prostate Cancer and Prostatic Diseases (2009) 12, 143–147; doi:10.1038/pcan.2008.47; published online 2 September 2008
Biopsy tissue microarray study of Ki-67 expression in untreated, localized prostate cancer managed by active surveillance
S Jhavar1, J Bartlett1, G Kovacs2, C Corbishley3, D Dearnaley1,4, R Eeles1,4, V Khoo4, R Huddart4, A Horwich4, A Thompson4, A Norman4, D Brewer1, C S Cooper1,5 and C Parker1,4,5
- 1Institute of Cancer Research, Male Urological Cancer Research Centre, Sutton, Surrey, UK
- 2Laboratory of Molecular Oncology, Medical Faculty, Reprecht-Karls-University, Heidelberg, Germany
- 3Department of Cellular Pathology, St Georges Hospital NHS Trust, Tooting, London, UK
- 4The Royal Marsden NHS Trust Foundation Trust, Sutton, Surrey, UK
Correspondence: Dr C Parker, Institute of Cancer Research and Royal Marsden Hospital NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, UK. E-mail: chris.parker@icr.ac.uk
5Joint last authors.
Received 11 April 2008; Revised 14 July 2008; Accepted 28 July 2008; Published online 2 September 2008.
Abstract
Active surveillance provides a unique opportunity to study biomarkers of prostate cancer behaviour, although only small volumes of tumor tissue are typically available. We have evaluated a technique for constructing tissue microarrays (TMAs) from needle biopsies for assessing immunohistochemical markers in localized prostate cancer managed by active surveillance. TMAs were constructed from diagnostic prostate biopsies for 60 patients with localized prostatic adenocarcinoma in a prospective cohort study of active surveillance. Radical treatment was recommended for a prostate-specific antigen (PSA) velocity greater than 1 ng ml-1 per year or adverse histology in repeat biopsies, defined as Gleason score
4+3 or >50% of cores involved. Sections from the TMAs were stained with H&E, P63/AMACR and Ki-67. Time to radical treatment was analysed with respect to clinical characteristics and Ki-67 LI. At a median follow up of 36 months, 25/60 (42%) patients had received radical treatment. On univariate analysis, PSA density (P=0.001), Gleason score (P=0.001), clinical T stage (P=0.01), Ki-67 LI (P=0.02) and initial PSA (P=0.04) were associated with time to radical treatment. On multivariate analysis, PSA density (P=0.01), Ki-67 LI (P=0.03) and Gleason score (P=0.04) were independent determinants of progression to radical treatment. TMAs constructed from prostate needle biopsies can be used to assess immunohistochemical markers in localized prostate cancer managed by active surveillance. Ki-67 LI merits further study as a possible biomarker of early prostate cancer behaviour.
Keywords:
needle biopsies, tissue microarray, Ki-67 antigen
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