{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:06:35Z","timestamp":1790179595259,"version":"4.1.0"},"reference-count":30,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dermatology"],"published-print":{"date-parts":[[2020]]},"abstract":"<b><i>Background:<\/i><\/b> Mammalian target of rapamycin (mTOR) inhibitors have been shown to have excellent effects in the management of kaposiform hemangioendothelioma (KHE); however, the mechanism of action is unclear. This study identified the expressions of mTOR pathway-related proteins in different vascular tumors to provide insight into the pathogenesis of KHE. <b><i>Methods:<\/i><\/b> We retrospectively reviewed the pathologic specimens of 30 patients (KHE, 15; tufted angioma [TA], 5; infantile hemangioma [IH], 5; and lymphatic malformation [LM], 5). The immunohistochemical expression of mTOR-related proteins tuberous sclerosis complex 2 (TSC2), phosphatase and tensin homologue (PTEN), phosphorylated eukaryotic translation initiation factor 4E binding protein 1 (p-4EBP1), phosphorylated mTOR (p-mTOR), and phosphorylated ribosomal protein S6 kinase B1 (p-P70S6K) were analyzed using Image-Pro Plus software. KHE had the following pattern of expression in the spindle vascular endothelial cells: TSC2 (\u2013); PTEN (\u2013); p-4EBP1 (+); p-mTOR (+); and p-P70S6K (+). <b><i>Results:<\/i><\/b> All 3 patients treated with sirolimus had good responses. The TA results were similar to KHE with no significant differences (p-4EBP1: <i>p<\/i> = 0.0687; p-mTOR: <i>p<\/i> = 0.0832). The expressions of TSC2, PTEN, p-4EBP1, p-mTOR, and p-P70S6K were negative or weakly positive in IH with a statistically significant difference compared to KHE (p-4EBP1: <i>p<\/i> &#x3c; 0.001; p-mTOR: <i>p<\/i> &#x3c; 0.001; p-P70S6K: <i>p<\/i> &#x3c; 0.001). LM had no significant differences when compared to KHE. <b><i>Conclusions:<\/i><\/b> The absence of TSC2 and PTEN caused abnormal activation of the mTOR signaling pathway and may be involved in the pathogenesis of KHE. The expression of mTOR-related proteins in TA and LM was similar to KHE, unlike IH. The KHE pattern of expression [PTEN (\u2013), TSC2 (\u2013), p-mTOR (+), p-P70S6K (+), and p-4EBP1 (+)] suggested that sirolimus may be a good therapeutic choice.<\/jats:p>","DOI":"10.1159\/000503604","type":"journal-article","created":{"date-parts":[[2020,1,2]],"date-time":"2020-01-02T22:00:32Z","timestamp":1578002432000},"page":"262-270","source":"Crossref","is-referenced-by-count":13,"title":["Immunohistochemical Analysis of mTOR Pathway-Related Proteins in Kaposiform Hemangioendothelioma"],"prefix":"10.1159","volume":"236","author":[{"given":"Zuopeng","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongqiang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2020,1,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199304000-00001"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-010-9331-1"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1309\/B8TC0LBVH8XY5MFV"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22766"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2017.04.023"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0b013e318281558e"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25296"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24103"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24957"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25979"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(98)70034-4"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1007\/s12154-008-0003-5"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa042831"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200405000-00001"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.16400"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.30775"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-013-1549-3"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1293\/tox.2017-0031"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2007.05.021"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdi113"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.3109\/08880018.2016.1160170"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S205160"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.06.127"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002112"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2011.00051"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20030755"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1039\/C5MB00101C"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.12.004"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0117440"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1111\/pde.12023"}],"container-title":["Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/503604","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/503604","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:02:00Z","timestamp":1745424120000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000503604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020]]},"references-count":30,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,5,6]]},"published-print":{"date-parts":[[2020,5,6]]}},"URL":"https:\/\/doi.org\/10.1159\/000503604","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.11493609","asserted-by":"subject"}]},"ISSN":["1018-8665","1421-9832"],"issn-type":[{"value":"1018-8665","type":"print"},{"value":"1421-9832","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020]]}}}