Immunohistochemical Analysis of mTOR Pathway-Related Proteins in Kaposiform Hemangioendothelioma.

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...

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Publicado en:Dermatology (10188665) Vol. 236; no. 3; pp. 262 - 271
Autores principales: Wang, Zuopeng, Zheng, Chao, Sun, Hongqiang, Yao, Wei, Li, Kai, Ma, Yangyang, Zheng, Shan
Formato: pictorial research tables/charts Journal Article
Publicado: Karger AG 2020
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 2020
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      pub: Karger AG
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        143156178
        10.1159/000503604
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        143156178
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        atl: Immunohistochemical Analysis of mTOR Pathway-Related Proteins in Kaposiform Hemangioendothelioma.
      aug:
        au:
          Wang, Zuopeng
          Zheng, Chao
          Sun, Hongqiang
          Yao, Wei
          Li, Kai
          Ma, Yangyang
          Zheng, Shan
        affil: Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China
      sug:
        subj:
          Immunohistochemistry Methods
          Kasabach-Merritt Syndrome Metabolism
          Hemangioma Metabolism
          Sarcoma, Kaposi's Metabolism
          Sirolimus Therapeutic Use
          Signal Transduction
          Antineoplastic Agents Therapeutic Use
          Kasabach-Merritt Syndrome Drug Therapy
          Lymphatic Abnormalities Metabolism
          Hemangioma Drug Therapy
          Epithelial Cells Metabolism
          Retrospective Design
          Sarcoma, Kaposi's Drug Therapy
          Human
      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.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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