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Nodal lymphangiogenesis and immunophenotypic variations of sinus endothelium in sentinel and non-sentinel lymph nodes of invasive breast carcinoma

Several studies have demonstrated the de novo formation of lymphatic vessels or the reorganization of lymphatic sinus in tumor-draining lymph nodes, partly preceding the detection of lymphatic metastases. This “lymphovascular niche”is supposed to facilitate the survival of metastatic tumor cells. Fe...

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Autores principales: Westhoff, Christina C., Müller, Sabrina K., Jank, Paul, Kalder, Matthias, Moll, Roland
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9873157/
https://www.ncbi.nlm.nih.gov/pubmed/36693068
http://dx.doi.org/10.1371/journal.pone.0280936
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author Westhoff, Christina C.
Müller, Sabrina K.
Jank, Paul
Kalder, Matthias
Moll, Roland
author_facet Westhoff, Christina C.
Müller, Sabrina K.
Jank, Paul
Kalder, Matthias
Moll, Roland
author_sort Westhoff, Christina C.
collection PubMed
description Several studies have demonstrated the de novo formation of lymphatic vessels or the reorganization of lymphatic sinus in tumor-draining lymph nodes, partly preceding the detection of lymphatic metastases. This “lymphovascular niche”is supposed to facilitate the survival of metastatic tumor cells. Few studies on nodal lymphangiogenesis in invasive breast cancer (BC) have been published, not considering tumor-free sentinel lymph nodes (SLN) and tumor types. Specimens of SLN and/ or non-SLN (NSLN) of 95 patients with BC were examined immunohistochemically for expression of the lymphatic endothelial marker D2-40 (podoplanin) on lymphatic vessels and the subcapsular sinus. The number of D2-40-positive lymph vessels in metastases was evaluated with two morphometric methods (Chalkley count and number per HPF). Data was explored with respect to TNM parameters, grading, tumor type, size of metastasis, lymph vessel number and hormone receptor/HER2 status with appropriate statistical tests. Lymphangiogenesis was detected exclusively in and around BC metastases with both methods for lymph vessel quantification being equivalent. Lymph vessel number correlated with the size of metastases, being significantly higher in larger metastases (p < 0.001). There was no significant statistical difference with respect to tumor types. Intranodal lymphangiogenesis could not be verified by D2-40 staining in any of the tumor-free lymph nodes examined. However, D2-40 was frequently detected in sinus endothelial/virgultar cells of the subcapsular sinus, partly with strong uniform positivity. Staining intensity and stained proportion of the subcapsular sinus were markedly heterogeneous, significantly correlating with each other both in SLN and NSLN (p < 0.001). A higher proportion of D2-40 stained subcapsular sinus in SLN was significantly associated with worse overall survival (p = 0.0036) and an independent prognostic parameter in multivariate analysis (p = 0.033, HR 2.87). Further studies are necessary to elucidate the biological and clinical significance of the observed immunophenotypic variations of nodal sinus endothelium.
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spelling pubmed-98731572023-01-25 Nodal lymphangiogenesis and immunophenotypic variations of sinus endothelium in sentinel and non-sentinel lymph nodes of invasive breast carcinoma Westhoff, Christina C. Müller, Sabrina K. Jank, Paul Kalder, Matthias Moll, Roland PLoS One Research Article Several studies have demonstrated the de novo formation of lymphatic vessels or the reorganization of lymphatic sinus in tumor-draining lymph nodes, partly preceding the detection of lymphatic metastases. This “lymphovascular niche”is supposed to facilitate the survival of metastatic tumor cells. Few studies on nodal lymphangiogenesis in invasive breast cancer (BC) have been published, not considering tumor-free sentinel lymph nodes (SLN) and tumor types. Specimens of SLN and/ or non-SLN (NSLN) of 95 patients with BC were examined immunohistochemically for expression of the lymphatic endothelial marker D2-40 (podoplanin) on lymphatic vessels and the subcapsular sinus. The number of D2-40-positive lymph vessels in metastases was evaluated with two morphometric methods (Chalkley count and number per HPF). Data was explored with respect to TNM parameters, grading, tumor type, size of metastasis, lymph vessel number and hormone receptor/HER2 status with appropriate statistical tests. Lymphangiogenesis was detected exclusively in and around BC metastases with both methods for lymph vessel quantification being equivalent. Lymph vessel number correlated with the size of metastases, being significantly higher in larger metastases (p < 0.001). There was no significant statistical difference with respect to tumor types. Intranodal lymphangiogenesis could not be verified by D2-40 staining in any of the tumor-free lymph nodes examined. However, D2-40 was frequently detected in sinus endothelial/virgultar cells of the subcapsular sinus, partly with strong uniform positivity. Staining intensity and stained proportion of the subcapsular sinus were markedly heterogeneous, significantly correlating with each other both in SLN and NSLN (p < 0.001). A higher proportion of D2-40 stained subcapsular sinus in SLN was significantly associated with worse overall survival (p = 0.0036) and an independent prognostic parameter in multivariate analysis (p = 0.033, HR 2.87). Further studies are necessary to elucidate the biological and clinical significance of the observed immunophenotypic variations of nodal sinus endothelium. Public Library of Science 2023-01-24 /pmc/articles/PMC9873157/ /pubmed/36693068 http://dx.doi.org/10.1371/journal.pone.0280936 Text en © 2023 Westhoff 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
Westhoff, Christina C.
Müller, Sabrina K.
Jank, Paul
Kalder, Matthias
Moll, Roland
Nodal lymphangiogenesis and immunophenotypic variations of sinus endothelium in sentinel and non-sentinel lymph nodes of invasive breast carcinoma
title Nodal lymphangiogenesis and immunophenotypic variations of sinus endothelium in sentinel and non-sentinel lymph nodes of invasive breast carcinoma
title_full Nodal lymphangiogenesis and immunophenotypic variations of sinus endothelium in sentinel and non-sentinel lymph nodes of invasive breast carcinoma
title_fullStr Nodal lymphangiogenesis and immunophenotypic variations of sinus endothelium in sentinel and non-sentinel lymph nodes of invasive breast carcinoma
title_full_unstemmed Nodal lymphangiogenesis and immunophenotypic variations of sinus endothelium in sentinel and non-sentinel lymph nodes of invasive breast carcinoma
title_short Nodal lymphangiogenesis and immunophenotypic variations of sinus endothelium in sentinel and non-sentinel lymph nodes of invasive breast carcinoma
title_sort nodal lymphangiogenesis and immunophenotypic variations of sinus endothelium in sentinel and non-sentinel lymph nodes of invasive breast carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9873157/
https://www.ncbi.nlm.nih.gov/pubmed/36693068
http://dx.doi.org/10.1371/journal.pone.0280936
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