PMID- 31896113
OWN - NLM
STAT- MEDLINE
DCOM- 20200911
LR  - 20211204
IS  - 1421-9832 (Electronic)
IS  - 1018-8665 (Linking)
VI  - 236
IP  - 3
DP  - 2020
TI  - Immunohistochemical Analysis of mTOR Pathway-Related Proteins in Kaposiform 
      Hemangioendothelioma.
PG  - 262-270
LID - 10.1159/000503604 [doi]
AB  - BACKGROUND: 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. METHODS: 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 (-); PTEN 
      (-); p-4EBP1 (+); p-mTOR (+); and p-P70S6K (+). RESULTS: All 3 patients treated 
      with sirolimus had good responses. The TA results were similar to KHE with no 
      significant differences (p-4EBP1: p = 0.0687; p-mTOR: p = 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: p < 0.001; p-mTOR: p < 0.001; p-P70S6K: p < 0.001). LM had no 
      significant differences when compared to KHE. CONCLUSIONS: 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 (-), 
      TSC2 (-), p-mTOR (+), p-P70S6K (+), and p-4EBP1 (+)] suggested that sirolimus may 
      be a good therapeutic choice.
CI  - (c) 2020 S. Karger AG, Basel.
FAU - Wang, Zuopeng
AU  - Wang Z
AD  - Department of Pediatric Surgery, Children's Hospital of Fudan University, 
      Shanghai, China.
FAU - Zheng, Chao
AU  - Zheng C
AD  - Department of Pediatric Surgery, Children's Hospital of Fudan University, 
      Shanghai, China.
FAU - Sun, Hongqiang
AU  - Sun H
AD  - Department of Pediatric Surgery, Shandong Dezhou People's Hospital, Shandong, 
      China.
FAU - Yao, Wei
AU  - Yao W
AD  - Department of Pediatric Surgery, Children's Hospital of Fudan University, 
      Shanghai, China.
FAU - Li, Kai
AU  - Li K
AD  - Department of Pediatric Surgery, Children's Hospital of Fudan University, 
      Shanghai, China, likai2727@163.com.
FAU - Ma, Yangyang
AU  - Ma Y
AD  - Department of Pathology, Children's Hospital of Fudan University, Shanghai, 
      China.
FAU - Zheng, Shan
AU  - Zheng S
AD  - Department of Pediatric Surgery, Children's Hospital of Fudan University, 
      Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20200102
PL  - Switzerland
TA  - Dermatology
JT  - Dermatology (Basel, Switzerland)
JID - 9203244
RN  - 0 (Antineoplastic Agents)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
RN  - Kaposiform Hemangioendothelioma
SB  - IM
MH  - Antineoplastic Agents/therapeutic use
MH  - Endothelial Cells/metabolism
MH  - Hemangioendothelioma/drug therapy/*metabolism
MH  - Hemangioma/metabolism
MH  - Humans
MH  - Immunohistochemistry/*methods
MH  - Kasabach-Merritt Syndrome/drug therapy/*metabolism
MH  - Lymphatic Abnormalities/metabolism
MH  - Retrospective Studies
MH  - Sarcoma, Kaposi/drug therapy/*metabolism
MH  - Signal Transduction
MH  - Sirolimus/therapeutic use
MH  - TOR Serine-Threonine Kinases/*biosynthesis/metabolism
OTO - NOTNLM
OT  - Immunohistochemistry
OT  - Kaposiform hemangioendothelioma
OT  - Mammalian target of rapamycin
OT  - Phosphatase and tensin homologue
EDAT- 2020/01/03 06:00
MHDA- 2020/09/12 06:00
CRDT- 2020/01/03 06:00
PHST- 2019/06/20 00:00 [received]
PHST- 2019/09/19 00:00 [accepted]
PHST- 2020/01/03 06:00 [pubmed]
PHST- 2020/09/12 06:00 [medline]
PHST- 2020/01/03 06:00 [entrez]
AID - 000503604 [pii]
AID - 10.1159/000503604 [doi]
PST - ppublish
SO  - Dermatology. 2020;236(3):262-270. doi: 10.1159/000503604. Epub 2020 Jan 2.