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The Lymphatic System in Endometriosis: a Pilot Study of Endometrial-Like Cells and Immune Cell Populations in Lymph Nodes Associated with Deep Infiltrating Bowel Lesions

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Abstract

In endometriosis, the lymphatic and immune systems are implicated in disease establishment and progression. The objective of this pilot study was to examine endometrial-like, and for the first time, immune cell populations in lymph nodes associated with deep infiltrating endometriosis (DIE) bowel lesions. Premenopausal women undergoing excision of endometriosis and/or hysterectomy were included. DIE bowel lesion-associated (n = 10) and other pelvic (n = 15) lymph nodes were studied. Samples were immunohistochemically stained for endometrial-like cells (CD10), T cells (CD3, CD4, CD8, and FoxP3), dendritic cells (DC; DC-Lamp and DC-Sign), B cells (CD20, CD79 and plasma), macrophages (CD68), and natural killer cells (NK; CD57). Cell abundance (percentage positive area) and antigen expression (optical density; OD) were quantified. Endometrial-like cells and each immune cell population were present in all studied nodes. The DIE bowel lesion-associated nodes showed features of immune activation, with T cell proliferation (CD3+ area p = 0.007, CD4+ area p = 0.015 compared with other pelvic nodes); and a mixture of helper and regulatory T cells, B cells, DCs, macrophages, and plasma cells present in the paracortex. In DIE bowel lesion-associated compared with other pelvic nodes, CD10+ endometrial-like cells were reduced (percentage positive area p < 0.001, OD p = 0.004). This study provides new insight into lymphatic and immune system involvement in advanced endometriosis. In particular, we have shown evidence of immune activation in DIE lesion-associated nodes. This was despite lower endometrial-like cell numbers compared with other pelvic nodes. The observations contribute to a developing understanding of the local immune response to advanced disease.

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Acknowledgments

The authors thank Professor Ian S. Fraser and Dr. Marina Berbic (Department of Obstetrics and Gynaecology, The University of New South Wales) for the useful comments in the project’s early stage, Dr. Georgina Luscombe (School of Rural Health, The University of Sydney) for the statistical advice, and Dr. Louise Cole (Bosch Institute Advanced Microscopy Facility, The University of Sydney) and Sanaz Maleki (Department of Pathology, The University of Sydney) for the technical support.

Funding

This study was financially supported by the Department of Obstetrics, Gynaecology and Neonatology, The University of Sydney. This study was performed at the Department of Obstetrics, Gynaecology and Neonatology, The University of Sydney.

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Authors and Affiliations

  1. The University of Sydney Obstetrics, Gynaecology and Neonatology; Central Clinical School; Faculty of Medicine and Health, Medical Foundation Building K25, The University of Sydney, Sydney, NSW, 2006, Australia

    Laila F. Jerman, Robert Markham & Alison J. Hey-Cunningham

  2. Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, NSW, 2050, Australia

    Lyndal Anderson

  3. The University of Sydney Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2006, Australia

    Lyndal Anderson

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  1. Laila F. Jerman
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Correspondence to Alison J. Hey-Cunningham.

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This study was approved by the Human Research Ethics Committees of the Sydney Local Health District (Royal Prince Alfred Hospital [RPAH] zone; Protocol number X13-00037, HREC/13/RPAH/52) and the University of Sydney (Project number 2013/496).

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Jerman, L.F., Anderson, L., Markham, R. et al. The Lymphatic System in Endometriosis: a Pilot Study of Endometrial-Like Cells and Immune Cell Populations in Lymph Nodes Associated with Deep Infiltrating Bowel Lesions. Reprod. Sci. 27, 977–987 (2020). https://doi.org/10.1007/s43032-020-00171-0

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