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Pixelwise H-score: A novel digital image analysis-based metric to quantify membrane biomarker expression from immunohistochemistry images

Immunohistochemistry (IHC) assays play a central role in evaluating biomarker expression in tissue sections for diagnostic and research applications. Manual scoring of IHC images, which is the current standard of practice, is known to have several shortcomings in terms of reproducibility and scalabi...

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Autores principales: Ram, Sripad, Vizcarra, Pamela, Whalen, Pamela, Deng, Shibing, Painter, C. L., Jackson-Fisher, Amy, Pirie-Shepherd, Steven, Xia, Xiaoling, Powell, Eric L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475990/
https://www.ncbi.nlm.nih.gov/pubmed/34570796
http://dx.doi.org/10.1371/journal.pone.0245638
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author Ram, Sripad
Vizcarra, Pamela
Whalen, Pamela
Deng, Shibing
Painter, C. L.
Jackson-Fisher, Amy
Pirie-Shepherd, Steven
Xia, Xiaoling
Powell, Eric L.
author_facet Ram, Sripad
Vizcarra, Pamela
Whalen, Pamela
Deng, Shibing
Painter, C. L.
Jackson-Fisher, Amy
Pirie-Shepherd, Steven
Xia, Xiaoling
Powell, Eric L.
author_sort Ram, Sripad
collection PubMed
description Immunohistochemistry (IHC) assays play a central role in evaluating biomarker expression in tissue sections for diagnostic and research applications. Manual scoring of IHC images, which is the current standard of practice, is known to have several shortcomings in terms of reproducibility and scalability to large scale studies. Here, by using a digital image analysis-based approach, we introduce a new metric called the pixelwise H-score (pix H-score) that quantifies biomarker expression from whole-slide scanned IHC images. The pix H-score is an unsupervised algorithm that only requires the specification of intensity thresholds for the biomarker and the nuclear-counterstain channels. We present the detailed implementation of the pix H-score in two different whole-slide image analysis software packages Visiopharm and HALO. We consider three biomarkers P-cadherin, PD-L1, and 5T4, and show how the pix H-score exhibits tight concordance to multiple orthogonal measurements of biomarker abundance such as the biomarker mRNA transcript and the pathologist H-score. We also compare the pix H-score to existing automated image analysis algorithms and demonstrate that the pix H-score provides either comparable or significantly better performance over these methodologies. We also present results of an empirical resampling approach to assess the performance of the pix H-score in estimating biomarker abundance from select regions within the tumor tissue relative to the whole tumor resection. We anticipate that the new metric will be broadly applicable to quantify biomarker expression from a wide variety of IHC images. Moreover, these results underscore the benefit of digital image analysis-based approaches which offer an objective, reproducible, and highly scalable strategy to quantitatively analyze IHC images.
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spelling pubmed-84759902021-09-28 Pixelwise H-score: A novel digital image analysis-based metric to quantify membrane biomarker expression from immunohistochemistry images Ram, Sripad Vizcarra, Pamela Whalen, Pamela Deng, Shibing Painter, C. L. Jackson-Fisher, Amy Pirie-Shepherd, Steven Xia, Xiaoling Powell, Eric L. PLoS One Research Article Immunohistochemistry (IHC) assays play a central role in evaluating biomarker expression in tissue sections for diagnostic and research applications. Manual scoring of IHC images, which is the current standard of practice, is known to have several shortcomings in terms of reproducibility and scalability to large scale studies. Here, by using a digital image analysis-based approach, we introduce a new metric called the pixelwise H-score (pix H-score) that quantifies biomarker expression from whole-slide scanned IHC images. The pix H-score is an unsupervised algorithm that only requires the specification of intensity thresholds for the biomarker and the nuclear-counterstain channels. We present the detailed implementation of the pix H-score in two different whole-slide image analysis software packages Visiopharm and HALO. We consider three biomarkers P-cadherin, PD-L1, and 5T4, and show how the pix H-score exhibits tight concordance to multiple orthogonal measurements of biomarker abundance such as the biomarker mRNA transcript and the pathologist H-score. We also compare the pix H-score to existing automated image analysis algorithms and demonstrate that the pix H-score provides either comparable or significantly better performance over these methodologies. We also present results of an empirical resampling approach to assess the performance of the pix H-score in estimating biomarker abundance from select regions within the tumor tissue relative to the whole tumor resection. We anticipate that the new metric will be broadly applicable to quantify biomarker expression from a wide variety of IHC images. Moreover, these results underscore the benefit of digital image analysis-based approaches which offer an objective, reproducible, and highly scalable strategy to quantitatively analyze IHC images. Public Library of Science 2021-09-27 /pmc/articles/PMC8475990/ /pubmed/34570796 http://dx.doi.org/10.1371/journal.pone.0245638 Text en © 2021 Ram et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ram, Sripad
Vizcarra, Pamela
Whalen, Pamela
Deng, Shibing
Painter, C. L.
Jackson-Fisher, Amy
Pirie-Shepherd, Steven
Xia, Xiaoling
Powell, Eric L.
Pixelwise H-score: A novel digital image analysis-based metric to quantify membrane biomarker expression from immunohistochemistry images
title Pixelwise H-score: A novel digital image analysis-based metric to quantify membrane biomarker expression from immunohistochemistry images
title_full Pixelwise H-score: A novel digital image analysis-based metric to quantify membrane biomarker expression from immunohistochemistry images
title_fullStr Pixelwise H-score: A novel digital image analysis-based metric to quantify membrane biomarker expression from immunohistochemistry images
title_full_unstemmed Pixelwise H-score: A novel digital image analysis-based metric to quantify membrane biomarker expression from immunohistochemistry images
title_short Pixelwise H-score: A novel digital image analysis-based metric to quantify membrane biomarker expression from immunohistochemistry images
title_sort pixelwise h-score: a novel digital image analysis-based metric to quantify membrane biomarker expression from immunohistochemistry images
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475990/
https://www.ncbi.nlm.nih.gov/pubmed/34570796
http://dx.doi.org/10.1371/journal.pone.0245638
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