{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T04:35:04Z","timestamp":1791866104937,"version":"4.3.4"},"reference-count":44,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Amsterdam Reproduction and Development research institute","award":["Type 1"],"award-info":[{"award-number":["Type 1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>There is evidence for increased angiogenesis in the (ectopic) endometrium of adenomyosis patients under the influence of vascular endothelial growth factor (VEGF). VEGF stimulates both angiogenesis and lymph-angiogenesis. However, information on lymph vessels in the (ectopic) endometrium of adenomyosis patients is lacking. In this retrospective matched case-control study, multiplex immunohistochemistry was performed on thirty-eight paraffin embedded specimens from premenopausal women who had undergone a hysterectomy at the Amsterdam UMC between 2001 and 2018 to investigate the evidence for (lymph) angiogenesis in the (ectopic) endometrium or myometrium of patients with adenomyosis versus controls with unrelated pathologies. Baseline characteristics of both groups were comparable. In the proliferative phase, the blood and lymph vessel densities were, respectively, higher in the ectopic and eutopic endometrium of patients with adenomyosis than in the endometrium of controls. The relative number of blood vessels without \u03b1-smooth muscle actinin (\u03b1 SMA) was higher in the eutopic and ectopic endometrium of adenomyosis patients versus controls. The level of VEGF staining intensity was highest in the myometrium but did not differ between patients with adenomyosis or controls. The results indicate increased angiogenesis and lymphangiogenesis in the (ectopic) endometrium affected by adenomyosis. The clinical relevance of our findings should be confirmed in prospective clinical studies.<\/jats:p>","DOI":"10.3390\/ijms23158434","type":"journal-article","created":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T23:37:29Z","timestamp":1659310649000},"page":"8434","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Increased Angiogenesis and Lymphangiogenesis in Adenomyosis Visualized by Multiplex Immunohistochemistry"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3842-5023","authenticated-orcid":false,"given":"Marissa J.","family":"Harmsen","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction and Development Research Institute, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arda","family":"Ardu\u00e7","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction and Development Research Institute, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9610-8064","authenticated-orcid":false,"given":"Maaike C. G.","family":"Bleeker","sequence":"additional","affiliation":[{"name":"Department of Pathology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda J. M.","family":"Juffermans","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction and Development Research Institute, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjan W.","family":"Griffioen","sequence":"additional","affiliation":[{"name":"Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Angiogenesis Laboratory, Department of Medical Oncology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina S.","family":"Jordanova","sequence":"additional","affiliation":[{"name":"Amsterdam Reproduction and Development Research Institute, 1105 AZ Amsterdam, The Netherlands"},{"name":"Center for Gynecologic Oncology Amsterdam, Amsterdam UMC Location Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Department of Urology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith A. F.","family":"Huirne","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction and Development Research Institute, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/0002-9378(72)90781-8","article-title":"The elusive adenomyosis of the uterus\u2014Revisited","volume":"112","author":"Bird","year":"1972","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.fertnstert.2012.06.044","article-title":"The pathophysiology of uterine adenomyosis: An update","volume":"98","author":"Benagiano","year":"2012","journal-title":"Fertil. 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