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Characterizing Trastuzumab-Induced Alterations in Intratumoral Heterogeneity with Quantitative Imaging and Immunohistochemistry in HER2+ Breast Cancer

The purpose of this study is to investigate imaging and histology-based measurements of intratumoral heterogeneity to evaluate early treatment response to targeted therapy in a murine model of HER2+ breast cancer. BT474 tumor-bearing mice (N = 30) were treated with trastuzumab or saline and imaged l...

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Autores principales: Syed, Anum K., Woodall, Ryan, Whisenant, Jennifer G., Yankeelov, Thomas E., Sorace, Anna G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260456/
https://www.ncbi.nlm.nih.gov/pubmed/30472501
http://dx.doi.org/10.1016/j.neo.2018.10.008
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author Syed, Anum K.
Woodall, Ryan
Whisenant, Jennifer G.
Yankeelov, Thomas E.
Sorace, Anna G.
author_facet Syed, Anum K.
Woodall, Ryan
Whisenant, Jennifer G.
Yankeelov, Thomas E.
Sorace, Anna G.
author_sort Syed, Anum K.
collection PubMed
description The purpose of this study is to investigate imaging and histology-based measurements of intratumoral heterogeneity to evaluate early treatment response to targeted therapy in a murine model of HER2+ breast cancer. BT474 tumor-bearing mice (N = 30) were treated with trastuzumab or saline and imaged longitudinally with either dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) or (18)F-fluoromisonidazole (FMISO) positron emission tomography (PET). At the imaging study end point (day 4 for MRI or 7 for PET), each tumor was excised for immunohistochemistry analysis. Voxel-based histogram analysis was performed on imaging-derived parametric maps (i.e., K(trans) and v(e) from DCE-MRI, SUV from (18)F-FMISO-PET) of the tumor region of interest to measure heterogeneity. Image processing and histogram analysis of whole tumor slice immunohistochemistry data were performed to validate the in vivo imaging findings. Trastuzumab-treated tumors had increased heterogeneity in quantitative imaging measures of cellularity (v(e)), with a mean Kolmogorov-Smirnov (K-S) distance of 0.32 (P = .05) between baseline and end point distributions. Trastuzumab-treated tumors had increased vascular heterogeneity (K(trans)) and decreased hypoxic heterogeneity (SUV), with a mean K-S distance of 0.42 (P < .01) and 0.46 (P = .047), respectively, between baseline and study end points. These observations were validated by whole-slice immunohistochemistry analysis with mean interquartile range of CD31 distributions of 1.72 for treated and 0.95 for control groups (P = .02). Quantitative longitudinal changes in tumor cellular and vascular heterogeneity in response to therapy may provide evidence for early prediction of response and guide therapy for patients with HER2+ breast cancer.
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spelling pubmed-62604562018-12-06 Characterizing Trastuzumab-Induced Alterations in Intratumoral Heterogeneity with Quantitative Imaging and Immunohistochemistry in HER2+ Breast Cancer Syed, Anum K. Woodall, Ryan Whisenant, Jennifer G. Yankeelov, Thomas E. Sorace, Anna G. Neoplasia Original article The purpose of this study is to investigate imaging and histology-based measurements of intratumoral heterogeneity to evaluate early treatment response to targeted therapy in a murine model of HER2+ breast cancer. BT474 tumor-bearing mice (N = 30) were treated with trastuzumab or saline and imaged longitudinally with either dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) or (18)F-fluoromisonidazole (FMISO) positron emission tomography (PET). At the imaging study end point (day 4 for MRI or 7 for PET), each tumor was excised for immunohistochemistry analysis. Voxel-based histogram analysis was performed on imaging-derived parametric maps (i.e., K(trans) and v(e) from DCE-MRI, SUV from (18)F-FMISO-PET) of the tumor region of interest to measure heterogeneity. Image processing and histogram analysis of whole tumor slice immunohistochemistry data were performed to validate the in vivo imaging findings. Trastuzumab-treated tumors had increased heterogeneity in quantitative imaging measures of cellularity (v(e)), with a mean Kolmogorov-Smirnov (K-S) distance of 0.32 (P = .05) between baseline and end point distributions. Trastuzumab-treated tumors had increased vascular heterogeneity (K(trans)) and decreased hypoxic heterogeneity (SUV), with a mean K-S distance of 0.42 (P < .01) and 0.46 (P = .047), respectively, between baseline and study end points. These observations were validated by whole-slice immunohistochemistry analysis with mean interquartile range of CD31 distributions of 1.72 for treated and 0.95 for control groups (P = .02). Quantitative longitudinal changes in tumor cellular and vascular heterogeneity in response to therapy may provide evidence for early prediction of response and guide therapy for patients with HER2+ breast cancer. Neoplasia Press 2018-11-23 /pmc/articles/PMC6260456/ /pubmed/30472501 http://dx.doi.org/10.1016/j.neo.2018.10.008 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Syed, Anum K.
Woodall, Ryan
Whisenant, Jennifer G.
Yankeelov, Thomas E.
Sorace, Anna G.
Characterizing Trastuzumab-Induced Alterations in Intratumoral Heterogeneity with Quantitative Imaging and Immunohistochemistry in HER2+ Breast Cancer
title Characterizing Trastuzumab-Induced Alterations in Intratumoral Heterogeneity with Quantitative Imaging and Immunohistochemistry in HER2+ Breast Cancer
title_full Characterizing Trastuzumab-Induced Alterations in Intratumoral Heterogeneity with Quantitative Imaging and Immunohistochemistry in HER2+ Breast Cancer
title_fullStr Characterizing Trastuzumab-Induced Alterations in Intratumoral Heterogeneity with Quantitative Imaging and Immunohistochemistry in HER2+ Breast Cancer
title_full_unstemmed Characterizing Trastuzumab-Induced Alterations in Intratumoral Heterogeneity with Quantitative Imaging and Immunohistochemistry in HER2+ Breast Cancer
title_short Characterizing Trastuzumab-Induced Alterations in Intratumoral Heterogeneity with Quantitative Imaging and Immunohistochemistry in HER2+ Breast Cancer
title_sort characterizing trastuzumab-induced alterations in intratumoral heterogeneity with quantitative imaging and immunohistochemistry in her2+ breast cancer
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260456/
https://www.ncbi.nlm.nih.gov/pubmed/30472501
http://dx.doi.org/10.1016/j.neo.2018.10.008
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