Expression of LGR5 in mammary myoepithelial cells and in triple-negative breast cancers

Abstract Lineage tracing in mice indicates that LGR5 is an adult stem cell marker in multiple organs, such as the intestine, stomach, hair follicles, ovary, and mammary glands. Despite many studies exploring the presence of LGR5 cells in human tissues, little is known about its expression profile in...

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Autores principales:	Hyun Ju Lee, Jae Kyung Myung, Hye Sung Kim, Dong Hui Lee, Hyun Su Go, Jae Hyuck Choi, Hyun Min Koh, Su-Jae Lee, Bogun Jang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0f82d807307c46eea89e6e8385e43a65
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spelling	oai:doaj.org-article:0f82d807307c46eea89e6e8385e43a652021-12-02T17:19:17ZExpression of LGR5 in mammary myoepithelial cells and in triple-negative breast cancers10.1038/s41598-021-97351-y2045-2322https://doaj.org/article/0f82d807307c46eea89e6e8385e43a652021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97351-yhttps://doaj.org/toc/2045-2322Abstract Lineage tracing in mice indicates that LGR5 is an adult stem cell marker in multiple organs, such as the intestine, stomach, hair follicles, ovary, and mammary glands. Despite many studies exploring the presence of LGR5 cells in human tissues, little is known about its expression profile in either human mammary tissue or pathological lesions. In this study we aim to investigate LGR5 expression in normal, benign, and malignant lesions of the human breast using RNA in situ hybridization. LGR5 expression has not been observed in normal lactiferous ducts and terminal duct lobular units, whereas LGR5-positive cells have been specifically observed in the basal myoepithelium of ducts in the regenerative tissues, ductal carcinoma in situ, and in ducts surrounded by invasive cancer cells. These findings suggest LGR5 marks facultative stem cells that are involved in post injury regeneration instead of homeostatic stem cells. LGR5 positivity was found in 3% (9 of 278 cases) of invasive breast cancers (BC), and it showed positive associations with higher histologic grades (P = 0.001) and T stages (P < 0.001), while having negative correlations with estrogen receptor (P < 0.001) and progesterone receptor (P < 0.001) expression. Remarkably, all LGR5-positive BC, except one, belong to triple-negative BC (TNBC), representing 24% (9 of 38 cases) of all of them. LGR5 histoscores have no correlations with EGFR, CK5/6, Ki-67, or P53 expression. Additionally, no β-catenin nuclear localization was observed in LGR5-positive BC, indicating that canonical Wnt pathway activation is less likely involved in LGR5 expression in BC. Our results demonstrate that LGR5 expression is induced in regenerative conditions in the myoepithelium of human mammary ducts and that its expression is only observed in TNBC subtype among all invasive BC. Further studies regarding the functional and prognostic impact of LGR5 in TNBC are warranted.Hyun Ju LeeJae Kyung MyungHye Sung KimDong Hui LeeHyun Su GoJae Hyuck ChoiHyun Min KohSu-Jae LeeBogun JangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hyun Ju Lee Jae Kyung Myung Hye Sung Kim Dong Hui Lee Hyun Su Go Jae Hyuck Choi Hyun Min Koh Su-Jae Lee Bogun Jang Expression of LGR5 in mammary myoepithelial cells and in triple-negative breast cancers
description	Abstract Lineage tracing in mice indicates that LGR5 is an adult stem cell marker in multiple organs, such as the intestine, stomach, hair follicles, ovary, and mammary glands. Despite many studies exploring the presence of LGR5 cells in human tissues, little is known about its expression profile in either human mammary tissue or pathological lesions. In this study we aim to investigate LGR5 expression in normal, benign, and malignant lesions of the human breast using RNA in situ hybridization. LGR5 expression has not been observed in normal lactiferous ducts and terminal duct lobular units, whereas LGR5-positive cells have been specifically observed in the basal myoepithelium of ducts in the regenerative tissues, ductal carcinoma in situ, and in ducts surrounded by invasive cancer cells. These findings suggest LGR5 marks facultative stem cells that are involved in post injury regeneration instead of homeostatic stem cells. LGR5 positivity was found in 3% (9 of 278 cases) of invasive breast cancers (BC), and it showed positive associations with higher histologic grades (P = 0.001) and T stages (P < 0.001), while having negative correlations with estrogen receptor (P < 0.001) and progesterone receptor (P < 0.001) expression. Remarkably, all LGR5-positive BC, except one, belong to triple-negative BC (TNBC), representing 24% (9 of 38 cases) of all of them. LGR5 histoscores have no correlations with EGFR, CK5/6, Ki-67, or P53 expression. Additionally, no β-catenin nuclear localization was observed in LGR5-positive BC, indicating that canonical Wnt pathway activation is less likely involved in LGR5 expression in BC. Our results demonstrate that LGR5 expression is induced in regenerative conditions in the myoepithelium of human mammary ducts and that its expression is only observed in TNBC subtype among all invasive BC. Further studies regarding the functional and prognostic impact of LGR5 in TNBC are warranted.
format	article
author	Hyun Ju Lee Jae Kyung Myung Hye Sung Kim Dong Hui Lee Hyun Su Go Jae Hyuck Choi Hyun Min Koh Su-Jae Lee Bogun Jang
author_facet	Hyun Ju Lee Jae Kyung Myung Hye Sung Kim Dong Hui Lee Hyun Su Go Jae Hyuck Choi Hyun Min Koh Su-Jae Lee Bogun Jang
author_sort	Hyun Ju Lee
title	Expression of LGR5 in mammary myoepithelial cells and in triple-negative breast cancers
title_short	Expression of LGR5 in mammary myoepithelial cells and in triple-negative breast cancers
title_full	Expression of LGR5 in mammary myoepithelial cells and in triple-negative breast cancers
title_fullStr	Expression of LGR5 in mammary myoepithelial cells and in triple-negative breast cancers
title_full_unstemmed	Expression of LGR5 in mammary myoepithelial cells and in triple-negative breast cancers
title_sort	expression of lgr5 in mammary myoepithelial cells and in triple-negative breast cancers
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0f82d807307c46eea89e6e8385e43a65
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Expression of LGR5 in mammary myoepithelial cells and in triple-negative breast cancers

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