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Immunohistochemical biomarker validation in highly selective needle biopsy microarrays derived from mpMRI-characterized prostates

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Title: Immunohistochemical biomarker validation in highly selective needle biopsy microarrays derived from mpMRI-characterized prostates
Authors: Olivier, J
Stavrinides, V
Kay, J
Freeman, A
Pye, H
Ahmed, Z
Carmona Echeverria, L
Heavey, S
Simmons, LAM
Kanthabalan, A
Arya, M
Briggs, T
Barratt, D
Charman, SC
Gelister, J
Hawkes, D
Hu, Y
Jameson, C
McCartan, N
Punwani, S
Van der Muelen, J
Moore, C
Emberton, M
Ahmed, HU
Whitaker, HC
Item Type: Journal Article
Abstract: INTRODUCTION: Diagnosing prostate cancer routinely involves tissue biopsy and increasingly image guided biopsy using multiparametric MRI (mpMRI). Excess tissue after diagnosis can be used for research to improve the diagnostic pathway and the vertical assembly of prostate needle biopsy cores into tissue microarrays (TMAs) allows the parallel immunohistochemical (IHC) validation of cancer biomarkers in routine diagnostic specimens. However, tissue within a biopsy core is often heterogeneous and cancer is not uniformly present, resulting in needle biopsy TMAs that suffer from highly variable cancer detection rates that complicate parallel biomarker validation. MATERIALS AND METHODS: The prostate cores with the highest tumor burden (in terms of Gleason score and/or maximum cancer core length) were obtained from 249 patients in the PICTURE trial who underwent transperineal template prostate mapping (TPM) biopsy at 5 mm intervals preceded by mpMRI. From each core, 2 mm segments containing tumor or benign tissue (as assessed on H&E pathology) were selected, excised and embedded vertically into a new TMA block. TMA sections were then IHC-stained for the routinely used prostate cancer biomarkers PSA, PSMA, AMACR, p63, and MSMB and assessed using the h-score method. H-scores in patient matched malignant and benign tissue were correlated with the Gleason grade of the original core and the MRI Likert score for the sampled prostate area. RESULTS: A total of 2240 TMA cores were stained and IHC h-scores were assigned to 1790. There was a statistically significant difference in h-scores between patient matched malignant and adjacent benign tissue that is independent of Likert score. There was no association between the h-scores and Gleason grade or Likert score within each of the benign or malignant groups. CONCLUSION: The construction of highly selective TMAs from prostate needle biopsy cores is possible. IHC data obtained through this method are highly reliable and can be correlated with imaging. IHC expression patterns for PSA, PSMA, AMACR, p63, and MSMB are distinct in malignant and adjacent benign tissue but did not correlate with mpMRI Likert score.
Issue Date: 1-Dec-2018
Date of Acceptance: 5-Jul-2018
URI: http://hdl.handle.net/10044/1/62064
DOI: https://dx.doi.org/10.1002/pros.23698
ISSN: 0270-4137
Publisher: Wiley
Start Page: 1229
End Page: 1237
Journal / Book Title: The Prostate
Volume: 78
Issue: 16
Copyright Statement: © 2018 Wiley Periodicals, Inc. This is the accepted version of an article which has been published in final form at https://dx.doi.org/10.1002/pros.23698
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: 204998/Z/16/Z
Keywords: Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
Urology & Nephrology
immunohistochemistry
MRI
prostate cancer
tissue microarrays
CONSTRUCTING TISSUE MICROARRAYS
DIAGNOSTIC-ACCURACY
CANCER
SPECIMENS
PATHOLOGY
MRI
immunohistochemistry
prostate cancer
tissue microarrays
Biomarkers, Tumor
Humans
Image-Guided Biopsy
Immunohistochemistry
Magnetic Resonance Imaging
Male
Neoplasm Grading
Prostate
Prostatic Neoplasms
Prostate
Humans
Prostatic Neoplasms
Magnetic Resonance Imaging
Immunohistochemistry
Male
Neoplasm Grading
Image-Guided Biopsy
Biomarkers, Tumor
MRI
immunohistochemistry
prostate cancer
tissue microarrays
Oncology & Carcinogenesis
1103 Clinical Sciences
1112 Oncology and Carcinogenesis
1114 Paediatrics and Reproductive Medicine
Publication Status: Published
Conference Place: United States
Online Publication Date: 2018-08-02
Appears in Collections:Department of Surgery and Cancer