Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jun;70(6):323-329.
doi: 10.1111/pin.12913. Epub 2020 Feb 18.

Analysis of mTOR pathway expression in lymphatic malformation and related diseases

Yumiko Hori  1 , Michio Ozeki  2 , Katsutoshi Hirose  3 , Kentaro Matsuoka  4 , Takahiro Matsui  1 , Masaharu Kohara  1 , Shinichiro Tahara  1 , Satoru Toyosawa  3 , Toshiyuki Fukao  2 , Eiichi Morii  1
Affiliations

Analysis of mTOR pathway expression in lymphatic malformation and related diseases

Yumiko Hori et al. Pathol Int. 2020 Jun.

Abstract

The mammalian target of rapamycin (mTOR) inhibitor sirolimus is an effective treatment for difficult-to-treat lymphatic anomalies. However, little is known about the expression of mTOR pathway components in lymphatic anomalies. Here we investigated the expression pattern of mTOR pathway components and their phosphorylated forms (mTOR, p-mTOR, 4EBP1, p-4EBP1, S6K1 and p-S6K1) in normal lymphatic vessels and lymphatic anomalies using immunohistochemistry. We studied 18 patients of lymphatic anomalies, including lymphatic malformation (LM, n = 14), Kaposiform lymphangiomatosis (KLA, n = 2) and Kaposiform hemangioendothelioma (KHE, n = 2). Normal lymphatic vessels expressed 4EBP1, S6K1 and p-S6K1, but not p-4EBP1, mTOR or p-mTOR. The mTOR was detected in all lymphatic anomalies, whereas its activation form p-mTOR was detected in half cases of KLA and KHE but not in LM. All lymphatic anomalies expressed S6K1 and its activated form p-S6K1. The expression of 4EBP1 was also found in all lymphatic anomalies, but its activation was detected in approximately half of them. The activation of mTOR was seen in tumor (KLA and KHE) but not in malformation (LM), whereas the activation of S6K1 and 4EBP1 was seen in all and half of lymphatic anomalies, respectively.

Keywords: 4EBP1; S6K1; lymphangiogenesis; lymphatic malformation; mTOR; rapamycin; sirolimus.

PubMed Disclaimer

References

REFERENCES

    1. Boscolo E, Coma S, Luks VL et al. AKT hyper-phosphorylation associated with PI3K mutations in lymphatic endothelial cells from a patient with lymphatic malformation. Angiogenesis 2015; 18: 151-62.
    1. Lim YH, Bacchiocchi A, Qiu J et al. GNA14 somatic mutation causes congenital and sporadic vascular tumors by MAPK activation. Am J Hum Genet 2016; 99: 443-50.
    1. Yesil S, Tanyildiz HG, Bozkurt C, Cakmakci E, Sahin G. Single-center experience with sirolimus therapy for vascular malformations. Pediatr Hematol Oncol 2016; 33: 219-25.
    1. Lackner H, Karastaneva A, Schwinger W et al. Sirolimus for the treatment of children with various complicated vascular anomalies. Eur J Pediatr 2015; 174: 1579-84.
    1. Wang Z, Li K, Yao W, Dong K, Xiao X, Zheng S. Successful treatment of kaposiform lymphangiomatosis with sirolimus. Pediatr Blood Cancer 2015; 62: 1291-93.

Substances

LinkOut - more resources