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Vascular measurements correlate with estrogen receptor status

BACKGROUND: Breast carcinoma can be classified as either Estrogen Receptor (ER) positive or negative by immunohistochemical phenotyping, although ER expression may vary from 1 to 100% of malignant cells within an ER + tumor. This is similar to genetic variability observed in other tumor types and is...

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Autores principales: Lloyd, Mark C, Alfarouk, Khalid O, Verduzco, Daniel, Bui, Marilyn M, Gillies, Robert J, Ibrahim, Muntaser E, Brown, Joel S, Gatenby, Robert A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012762/
https://www.ncbi.nlm.nih.gov/pubmed/24755315
http://dx.doi.org/10.1186/1471-2407-14-279
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author Lloyd, Mark C
Alfarouk, Khalid O
Verduzco, Daniel
Bui, Marilyn M
Gillies, Robert J
Ibrahim, Muntaser E
Brown, Joel S
Gatenby, Robert A
author_facet Lloyd, Mark C
Alfarouk, Khalid O
Verduzco, Daniel
Bui, Marilyn M
Gillies, Robert J
Ibrahim, Muntaser E
Brown, Joel S
Gatenby, Robert A
author_sort Lloyd, Mark C
collection PubMed
description BACKGROUND: Breast carcinoma can be classified as either Estrogen Receptor (ER) positive or negative by immunohistochemical phenotyping, although ER expression may vary from 1 to 100% of malignant cells within an ER + tumor. This is similar to genetic variability observed in other tumor types and is generally viewed as a consequence of intratumoral evolution driven by random genetic mutations. Here we view cellular evolution within tumors as a classical Darwinian system in which variations in molecular properties represent predictable adaptations to spatially heterogeneous environmental selection forces. We hypothesize that ER expression is a successful adaptive strategy only if estrogen is present in the microenvironment. Since the dominant source of estrogen is blood flow, we hypothesized that, in general, intratumoral regions with higher blood flow would contain larger numbers of ER + cells when compared to areas of low blood flow and in turn necrosis. METHODS: This study used digital pathology whole slide image acquisition and advanced image analysis algorithms. We examined the spatial distribution of ER + and ER- cells, vascular density, vessel area, and tissue necrosis within histological sections of 24 breast cancer specimens. These data were correlated with the patients ER status and molecular pathology report findings. RESULTS: ANOVA analyses revealed a strong correlation between vascular area and ER expression and between high fractional necrosis and absent ER expression (R(2) = 39%; p < 0.003 and R(2) = 46%; p < 0.001), respectively). ER expression did not correlate with tumor grade or size. CONCLUSION: We conclude that ER expression can be understood as a Darwinian process and linked to variations in estrogen delivery by temporal and spatial heterogeneity in blood flow. This correlation suggests strategies to promote intratumoral blood flow or a cyclic introduction of estrogen in the treatment schedule could be explored as a counter-intuitive approach to increase the efficacy of anti-estrogen drugs.
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spelling pubmed-40127622014-05-08 Vascular measurements correlate with estrogen receptor status Lloyd, Mark C Alfarouk, Khalid O Verduzco, Daniel Bui, Marilyn M Gillies, Robert J Ibrahim, Muntaser E Brown, Joel S Gatenby, Robert A BMC Cancer Research Article BACKGROUND: Breast carcinoma can be classified as either Estrogen Receptor (ER) positive or negative by immunohistochemical phenotyping, although ER expression may vary from 1 to 100% of malignant cells within an ER + tumor. This is similar to genetic variability observed in other tumor types and is generally viewed as a consequence of intratumoral evolution driven by random genetic mutations. Here we view cellular evolution within tumors as a classical Darwinian system in which variations in molecular properties represent predictable adaptations to spatially heterogeneous environmental selection forces. We hypothesize that ER expression is a successful adaptive strategy only if estrogen is present in the microenvironment. Since the dominant source of estrogen is blood flow, we hypothesized that, in general, intratumoral regions with higher blood flow would contain larger numbers of ER + cells when compared to areas of low blood flow and in turn necrosis. METHODS: This study used digital pathology whole slide image acquisition and advanced image analysis algorithms. We examined the spatial distribution of ER + and ER- cells, vascular density, vessel area, and tissue necrosis within histological sections of 24 breast cancer specimens. These data were correlated with the patients ER status and molecular pathology report findings. RESULTS: ANOVA analyses revealed a strong correlation between vascular area and ER expression and between high fractional necrosis and absent ER expression (R(2) = 39%; p < 0.003 and R(2) = 46%; p < 0.001), respectively). ER expression did not correlate with tumor grade or size. CONCLUSION: We conclude that ER expression can be understood as a Darwinian process and linked to variations in estrogen delivery by temporal and spatial heterogeneity in blood flow. This correlation suggests strategies to promote intratumoral blood flow or a cyclic introduction of estrogen in the treatment schedule could be explored as a counter-intuitive approach to increase the efficacy of anti-estrogen drugs. BioMed Central 2014-04-23 /pmc/articles/PMC4012762/ /pubmed/24755315 http://dx.doi.org/10.1186/1471-2407-14-279 Text en Copyright © 2014 Lloyd et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
spellingShingle Research Article
Lloyd, Mark C
Alfarouk, Khalid O
Verduzco, Daniel
Bui, Marilyn M
Gillies, Robert J
Ibrahim, Muntaser E
Brown, Joel S
Gatenby, Robert A
Vascular measurements correlate with estrogen receptor status
title Vascular measurements correlate with estrogen receptor status
title_full Vascular measurements correlate with estrogen receptor status
title_fullStr Vascular measurements correlate with estrogen receptor status
title_full_unstemmed Vascular measurements correlate with estrogen receptor status
title_short Vascular measurements correlate with estrogen receptor status
title_sort vascular measurements correlate with estrogen receptor status
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012762/
https://www.ncbi.nlm.nih.gov/pubmed/24755315
http://dx.doi.org/10.1186/1471-2407-14-279
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