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Technical Feasibility of Tissue Microarray (TMA) Analysis of Tumor-Associated Immune Response in Prostate Cancer

Introduction: The androgen receptor (AR) regulates immune-related epithelial-to-mesenchymal transition (EMT), and prostate cancer (PCa) metastasis. Primary tumor-infiltrating lymphocytes (TILs) [CD3(+), CD4(+), and CD8(+) TILs] are potential prognostic indicators in PCa, and variations may contribut...

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Autores principales: Wallace, Timothy J., Qian, Junqi, Avital, Itzhak, Bay, Curt, Man, Yan-Gao, Wellman, Laurie L., Moskaluk, Chris, Troyer, Dean, Ramnani, Dharam, Stojadinovic, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010688/
https://www.ncbi.nlm.nih.gov/pubmed/29937939
http://dx.doi.org/10.7150/jca.22846
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author Wallace, Timothy J.
Qian, Junqi
Avital, Itzhak
Bay, Curt
Man, Yan-Gao
Wellman, Laurie L.
Moskaluk, Chris
Troyer, Dean
Ramnani, Dharam
Stojadinovic, Alexander
author_facet Wallace, Timothy J.
Qian, Junqi
Avital, Itzhak
Bay, Curt
Man, Yan-Gao
Wellman, Laurie L.
Moskaluk, Chris
Troyer, Dean
Ramnani, Dharam
Stojadinovic, Alexander
author_sort Wallace, Timothy J.
collection PubMed
description Introduction: The androgen receptor (AR) regulates immune-related epithelial-to-mesenchymal transition (EMT), and prostate cancer (PCa) metastasis. Primary tumor-infiltrating lymphocytes (TILs) [CD3(+), CD4(+), and CD8(+) TILs] are potential prognostic indicators in PCa, and variations may contribute to racial disparities in tumor biology and PCa outcomes. Aim: To assess the technical feasibility of tumor microarray (TMA)-based methods to perform multi-marker TIL profiling in primary resected PCa. Methods: Paraffin-embedded tissue cores of histopathologically-confirmed primary PCa (n = 40; 1 TMA tissue specimen loss) were arrayed in triplicate on TMAs. Expression profiles of AR, CD3(+), CD4(+), and CD8(+) TILs in normal prostate, and the center and periphery of both the tumor-dominant nodule and highest Gleason grade were detected by IHC and associated with clinical and pathological data using standard statistical methodology. An independent pathologist, blinded to the clinical data, scored all samples (percent and intensity of positive cells). Results: TMAs were constructed from 21 (53.8%) Black and 18 (46.2%) White males with completely-resected, primarily pT2 stage PCa [pT2a (n = 3; 7.7%); pT2b (n = 2; 5.1%); pT2c (n = 27; 69.2%); pT3a (n = 5; 12.8%); mean pre-op PSA = 8.17 ng/ml]. The CD3, CD4, CD8, and CD8/CD3 cellular protein expression differed from normal in the periphery of the dominant nodule, the center of the highest Gleason grade, and the periphery of the highest Gleason grade (P < 0.05). Correlations between TIL expression in the center and periphery of the dominant nodule, with corresponding center and periphery of the highest Gleason grade, respectively, were robust, and the magnitude of these correlations differed markedly by race (P < 0.05). Conclusions: Multi-marker (AR, CD3, CD4, CD8) profiling with IHC analysis of TMAs consisting of primary, non-metastatic resected prostate cancer is technically feasible in this pilot study. Future studies will evaluate primary tumor immunoscore using semi-quantitative, IHC-based methodology to assess differences in the spectrum, quantity, and/or localization of TILs, and to gain insights into racial disparities in PCa tumor biology and clinical outcomes.
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spelling pubmed-60106882018-06-22 Technical Feasibility of Tissue Microarray (TMA) Analysis of Tumor-Associated Immune Response in Prostate Cancer Wallace, Timothy J. Qian, Junqi Avital, Itzhak Bay, Curt Man, Yan-Gao Wellman, Laurie L. Moskaluk, Chris Troyer, Dean Ramnani, Dharam Stojadinovic, Alexander J Cancer Research Paper Introduction: The androgen receptor (AR) regulates immune-related epithelial-to-mesenchymal transition (EMT), and prostate cancer (PCa) metastasis. Primary tumor-infiltrating lymphocytes (TILs) [CD3(+), CD4(+), and CD8(+) TILs] are potential prognostic indicators in PCa, and variations may contribute to racial disparities in tumor biology and PCa outcomes. Aim: To assess the technical feasibility of tumor microarray (TMA)-based methods to perform multi-marker TIL profiling in primary resected PCa. Methods: Paraffin-embedded tissue cores of histopathologically-confirmed primary PCa (n = 40; 1 TMA tissue specimen loss) were arrayed in triplicate on TMAs. Expression profiles of AR, CD3(+), CD4(+), and CD8(+) TILs in normal prostate, and the center and periphery of both the tumor-dominant nodule and highest Gleason grade were detected by IHC and associated with clinical and pathological data using standard statistical methodology. An independent pathologist, blinded to the clinical data, scored all samples (percent and intensity of positive cells). Results: TMAs were constructed from 21 (53.8%) Black and 18 (46.2%) White males with completely-resected, primarily pT2 stage PCa [pT2a (n = 3; 7.7%); pT2b (n = 2; 5.1%); pT2c (n = 27; 69.2%); pT3a (n = 5; 12.8%); mean pre-op PSA = 8.17 ng/ml]. The CD3, CD4, CD8, and CD8/CD3 cellular protein expression differed from normal in the periphery of the dominant nodule, the center of the highest Gleason grade, and the periphery of the highest Gleason grade (P < 0.05). Correlations between TIL expression in the center and periphery of the dominant nodule, with corresponding center and periphery of the highest Gleason grade, respectively, were robust, and the magnitude of these correlations differed markedly by race (P < 0.05). Conclusions: Multi-marker (AR, CD3, CD4, CD8) profiling with IHC analysis of TMAs consisting of primary, non-metastatic resected prostate cancer is technically feasible in this pilot study. Future studies will evaluate primary tumor immunoscore using semi-quantitative, IHC-based methodology to assess differences in the spectrum, quantity, and/or localization of TILs, and to gain insights into racial disparities in PCa tumor biology and clinical outcomes. Ivyspring International Publisher 2018-06-04 /pmc/articles/PMC6010688/ /pubmed/29937939 http://dx.doi.org/10.7150/jca.22846 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Wallace, Timothy J.
Qian, Junqi
Avital, Itzhak
Bay, Curt
Man, Yan-Gao
Wellman, Laurie L.
Moskaluk, Chris
Troyer, Dean
Ramnani, Dharam
Stojadinovic, Alexander
Technical Feasibility of Tissue Microarray (TMA) Analysis of Tumor-Associated Immune Response in Prostate Cancer
title Technical Feasibility of Tissue Microarray (TMA) Analysis of Tumor-Associated Immune Response in Prostate Cancer
title_full Technical Feasibility of Tissue Microarray (TMA) Analysis of Tumor-Associated Immune Response in Prostate Cancer
title_fullStr Technical Feasibility of Tissue Microarray (TMA) Analysis of Tumor-Associated Immune Response in Prostate Cancer
title_full_unstemmed Technical Feasibility of Tissue Microarray (TMA) Analysis of Tumor-Associated Immune Response in Prostate Cancer
title_short Technical Feasibility of Tissue Microarray (TMA) Analysis of Tumor-Associated Immune Response in Prostate Cancer
title_sort technical feasibility of tissue microarray (tma) analysis of tumor-associated immune response in prostate cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010688/
https://www.ncbi.nlm.nih.gov/pubmed/29937939
http://dx.doi.org/10.7150/jca.22846
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