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Vascularization of colorectal carcinoma liver metastasis: insight into stratification of patients for anti‐angiogenic therapies

Current treatment for metastatic disease targets angiogenesis. With the increasing data demonstrating that cancer cells do not entirely rely on angiogenesis but hijack the existing vasculature through mechanisms such as co‐option of existing blood vessels, identification of targets has become of utm...

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Autores principales: Lazaris, Anthoula, Amri, Abdellatif, Petrillo, Stephanie K, Zoroquiain, Paublo, Ibrahim, Nisreen, Salman, Ayat, Gao, Zu‐Hua, Vermeulen, Peter B, Metrakos, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065118/
https://www.ncbi.nlm.nih.gov/pubmed/29654716
http://dx.doi.org/10.1002/cjp2.100
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author Lazaris, Anthoula
Amri, Abdellatif
Petrillo, Stephanie K
Zoroquiain, Paublo
Ibrahim, Nisreen
Salman, Ayat
Gao, Zu‐Hua
Vermeulen, Peter B
Metrakos, Peter
author_facet Lazaris, Anthoula
Amri, Abdellatif
Petrillo, Stephanie K
Zoroquiain, Paublo
Ibrahim, Nisreen
Salman, Ayat
Gao, Zu‐Hua
Vermeulen, Peter B
Metrakos, Peter
author_sort Lazaris, Anthoula
collection PubMed
description Current treatment for metastatic disease targets angiogenesis. With the increasing data demonstrating that cancer cells do not entirely rely on angiogenesis but hijack the existing vasculature through mechanisms such as co‐option of existing blood vessels, identification of targets has become of utmost importance. Our study looks at the vasculature of chemonaïve and treated colorectal carcinoma liver metastases (CRCLMs) to obtain a basic understanding of the microvessel density, type of vasculature (mature versus immature), and correlation with histopathological growth patterns that demonstrate unique patterns of angiogenesis. We performed immunohistochemistry on chemonaïve sections of desmoplastic histopathological growth pattern (DHGP) and replacement histopathological growth patterns (RHGP) lesions with CD31 [endothelial cell (EC) marker] and CD34/Ki67 double staining, which denotes proliferating ECs. The CD31 stains demonstrated a lower microvascular CD31 +ve capillary density in the DHGP versus RHGP lesions; and integrating both immunostains with CD34/Ki67 staining on serial sections revealed proliferating vessels in DHGP lesions and co‐option of mature existing blood vessels in RHGP lesions. Interestingly, upon treatment with chemotherapy and bevacizumab, the RHGP lesions showed no necrosis whereas the DHGP lesions had almost 100% necrosis of the cancer cells and in most cases there was a single layer of viable cancer cells, just under or within the desmoplastic ring. The survival of these cells may be directly related to spatial location and possibly a different microenvironment, which may involve adhesion to different extracellular matrix components and/or different oxygen/nutrient availability. This remains to be elucidated. We provide evidence that DHGP CRCLMs obtain their blood supply via sprouting angiogenesis whereas RHGP lesions obtain their blood supply via co‐option of existing vasculature. Furthermore current treatment regimens do not affect RHGP lesions and although they kill the majority of the cancer cells in DHGP lesions, there are cells surviving within or adjacent to the desmoplastic ring which could potentially give rise to a growing lesion.
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spelling pubmed-60651182018-08-02 Vascularization of colorectal carcinoma liver metastasis: insight into stratification of patients for anti‐angiogenic therapies Lazaris, Anthoula Amri, Abdellatif Petrillo, Stephanie K Zoroquiain, Paublo Ibrahim, Nisreen Salman, Ayat Gao, Zu‐Hua Vermeulen, Peter B Metrakos, Peter J Pathol Clin Res Original Articles Current treatment for metastatic disease targets angiogenesis. With the increasing data demonstrating that cancer cells do not entirely rely on angiogenesis but hijack the existing vasculature through mechanisms such as co‐option of existing blood vessels, identification of targets has become of utmost importance. Our study looks at the vasculature of chemonaïve and treated colorectal carcinoma liver metastases (CRCLMs) to obtain a basic understanding of the microvessel density, type of vasculature (mature versus immature), and correlation with histopathological growth patterns that demonstrate unique patterns of angiogenesis. We performed immunohistochemistry on chemonaïve sections of desmoplastic histopathological growth pattern (DHGP) and replacement histopathological growth patterns (RHGP) lesions with CD31 [endothelial cell (EC) marker] and CD34/Ki67 double staining, which denotes proliferating ECs. The CD31 stains demonstrated a lower microvascular CD31 +ve capillary density in the DHGP versus RHGP lesions; and integrating both immunostains with CD34/Ki67 staining on serial sections revealed proliferating vessels in DHGP lesions and co‐option of mature existing blood vessels in RHGP lesions. Interestingly, upon treatment with chemotherapy and bevacizumab, the RHGP lesions showed no necrosis whereas the DHGP lesions had almost 100% necrosis of the cancer cells and in most cases there was a single layer of viable cancer cells, just under or within the desmoplastic ring. The survival of these cells may be directly related to spatial location and possibly a different microenvironment, which may involve adhesion to different extracellular matrix components and/or different oxygen/nutrient availability. This remains to be elucidated. We provide evidence that DHGP CRCLMs obtain their blood supply via sprouting angiogenesis whereas RHGP lesions obtain their blood supply via co‐option of existing vasculature. Furthermore current treatment regimens do not affect RHGP lesions and although they kill the majority of the cancer cells in DHGP lesions, there are cells surviving within or adjacent to the desmoplastic ring which could potentially give rise to a growing lesion. John Wiley and Sons Inc. 2018-04-14 /pmc/articles/PMC6065118/ /pubmed/29654716 http://dx.doi.org/10.1002/cjp2.100 Text en © 2018 The Authors The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Lazaris, Anthoula
Amri, Abdellatif
Petrillo, Stephanie K
Zoroquiain, Paublo
Ibrahim, Nisreen
Salman, Ayat
Gao, Zu‐Hua
Vermeulen, Peter B
Metrakos, Peter
Vascularization of colorectal carcinoma liver metastasis: insight into stratification of patients for anti‐angiogenic therapies
title Vascularization of colorectal carcinoma liver metastasis: insight into stratification of patients for anti‐angiogenic therapies
title_full Vascularization of colorectal carcinoma liver metastasis: insight into stratification of patients for anti‐angiogenic therapies
title_fullStr Vascularization of colorectal carcinoma liver metastasis: insight into stratification of patients for anti‐angiogenic therapies
title_full_unstemmed Vascularization of colorectal carcinoma liver metastasis: insight into stratification of patients for anti‐angiogenic therapies
title_short Vascularization of colorectal carcinoma liver metastasis: insight into stratification of patients for anti‐angiogenic therapies
title_sort vascularization of colorectal carcinoma liver metastasis: insight into stratification of patients for anti‐angiogenic therapies
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065118/
https://www.ncbi.nlm.nih.gov/pubmed/29654716
http://dx.doi.org/10.1002/cjp2.100
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