Construction of tissue microarrays from prostate needle biopsy specimens

Jhavar, Sameer; Corbishley, Catherine M.; Dearnaley, David P.; Fisher, Cyril; Falconer, Alison; Parker, Chris; Eeles, Rosalind; Cooper, Christopher S.

doi:10.1038/sj.bjc.6602726

Cited by 35 publications

(54 citation statements)

References 23 publications

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“…For each patient, cancerous regions from between 1 and 5 biopsy cores of the diagnostic samples were assembled on a biopsy TMA as described previously. 8 All patients consented for their pathological specimens to be used for research.…”

Section: Clinical Samplesmentioning

confidence: 99%

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Biopsy tissue microarray study of Ki-67 expression in untreated, localized prostate cancer managed by active surveillance

Jhavar

Bartlett

Kovács

et al. 2008

Prostate Cancer Prostatic Dis

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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 À1 per year or adverse histology in repeat biopsies, defined as Gleason score X4 þ 3 or 450% 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 ¼ 0.001), Gleason score (P ¼ 0.001), clinical T stage (P ¼ 0.01), Ki-67 LI (P ¼ 0.02) and initial PSA (P ¼ 0.04) were associated with time to radical treatment. On multivariate analysis, PSA density (P ¼ 0.01), Ki-67 LI (P ¼ 0.03) and Gleason score (P ¼ 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.

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Section: Clinical Samplesmentioning

confidence: 99%

“…7 We have previously described a 'checkerboard' technique for constructing TMAs from needle biopsy specimens. 8 To date, the biopsy TMA technique has not been applied to the small volume cancers managed by active surveillance.…”

Section: Introductionmentioning

confidence: 99%

Biopsy tissue microarray study of Ki-67 expression in untreated, localized prostate cancer managed by active surveillance

Jhavar

Bartlett

Kovács

et al. 2008

Prostate Cancer Prostatic Dis

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“…The biopsy TMA was constructed from pretreatment prostate biopsies using a "checkerboard" technique as previously described (31). Benign and malignant prostate tissues within each core were denoted for dissection based on hematoxylin and eosin (H&E)-stained sections by an experienced genitourinary pathologist (T. van der Kwast).…”

Section: Tma and Ihcmentioning

confidence: 99%

TMPRSS2-ERG Status Is Not Prognostic Following Prostate Cancer Radiotherapy: Implications for Fusion Status and DSB Repair

Pra

Lalonde

Sykes

et al. 2013

Clinical Cancer Research

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Background: Preclinical data suggest that TMPRSS2-ERG gene fusions, present in about 50% of prostate cancers, may be a surrogate for DNA repair status and therefore a biomarker for DNA-damaging agents. To test this hypothesis, we examined whether TMPRSS2-ERG status was associated with biochemical failure after clinical induction of DNA damage following image-guided radiotherapy (IGRT).Methods: Pretreatment biopsies from two cohorts of patients with intermediate-risk prostate cancer [T1/T2, Gleason score (GS) < 8, prostate-specific antigen (PSA) < 20 ng/mL; >7 years follow-up] were analyzed: (i) 126 patients [comparative genomic hybridization (CGH) cohort] with DNA samples assayed by array CGH (aCGH) for the TMPRSS2-ERG fusion; and (ii) 118 patients [immunohistochemical (IHC) cohort] whose biopsy samples were scored within a defined tissue microarray (TMA) immunostained for ERG overexpression (known surrogate for TMPRSS2-ERG fusion). Patients were treated with IGRT with a median dose of 76 Gy. The potential role of TMPRSS2-ERG status as a prognostic factor for biochemical relapse-free rate (bRFR; nadir þ 2 ng/mL) was evaluated in the context of clinical prognostic factors in multivariate analyses using a Cox proportional hazards model.Results: TMPRSS2-ERG fusion by aCGH was identified in 27 (21%) of the cases in the CGH cohort, and ERG overexpression was found in 59 (50%) patients in the IHC cohort. In both cohorts, TMPRSS2-ERG status was not associated with bRFR on univariate or multivariate analysis.Conclusions: In two similarly treated IGRT cohorts, TMPRSS2-ERG status was not prognostic for bRFR, in disagreement with the hypothesis that these prostate cancers have DNA repair defects that render them clinically more radiosensitive. TMPRSS2-ERG is therefore unlikely to be a predictive factor for IGRT response.

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“…In each method, we reorientate the biopsies into a vertical orientation allowing construction of biopsy TMAs and subsequent analysis of the markers in cross-sections taken from each biopsy TMA. In our original technique, a maximum of 20 biopsy specimens could be included within each TMA 2. A particular problem with this method is that the cutting out of small regular ‘checkers’ of wax containing a segment of the biopsy on one face, which is required for the construction of the biopsy TMA, is technically demanding and time-consuming.…”

Section: Introductionmentioning

confidence: 99%

High-density tissue microarrays from prostate needle biopsies

et al. 2010

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BackgroundFormalin-fixed prostate biopsies are frequently the only tissue collected at the time of prostate cancer diagnosis. There is therefore a requirement for techniques that allow the use of these prostate biopsy specimens in a high-throughput analysis of immunohistochemical and fluorescence-in-situ-hybridisation-detected biomarkers.MethodsThe authors have previously described methods that allow tissue microarray (TMA) construction from prostate biopsies. Here, we describe significant technical innovations that provide an easier and more robust system of biopsy–TMA construction.Results and discussionThe TMAs produced are of a high density (up to 104 cores each, 8×13) and allow a multiplex analysis of biomarkers in the context of clinical trials.

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Construction of tissue microarrays from prostate needle biopsy specimens

Cited by 35 publications

References 23 publications

Biopsy tissue microarray study of Ki-67 expression in untreated, localized prostate cancer managed by active surveillance

Biopsy tissue microarray study of Ki-67 expression in untreated, localized prostate cancer managed by active surveillance

TMPRSS2-ERG Status Is Not Prognostic Following Prostate Cancer Radiotherapy: Implications for Fusion Status and DSB Repair

High-density tissue microarrays from prostate needle biopsies

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