کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5716327 1606645 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Original contributionmTOR, VEGF, PDGFR, and c-kit signaling pathway activation in Kaposi sarcoma★
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی آسیب‌شناسی و فناوری پزشکی
پیش نمایش صفحه اول مقاله
Original contributionmTOR, VEGF, PDGFR, and c-kit signaling pathway activation in Kaposi sarcoma★
چکیده انگلیسی


- Kaposi sarcoma is tested for upregulation of mTOR, PDGF, VEGF, and c-kit pathways.
- Most express VEGF, c-kit, pS6, and PDGFB by immunohistochemistry.
- pS6, downstream of mTOR, is expressed strongly in most (67.3%) Kaposi sarcomas.
- Overexpression is independent of CD4 T-cell count in HIV-associated cases.
- Results support the use of targeted inhibitors for management of Kaposi sarcoma.

SummaryKaposi sarcoma (KS) is a locally progressive, intermediate-grade vascular neoplasm with no known cure, high recurrence rates, and potential for wide dissemination. Low efficacy and high toxicity limit current therapeutic options for advanced disease. Activation of mammalian target of rapamycin (mTOR), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and c-kit signaling pathways has been implicated in KS pathogenesis and may suggest a role for targeted inhibitors. KS cases were retrospectively retrieved (N = 274), most (90%) associated with human immunodeficiency virus. Tissue microarray slides were stained with human herpes virus-8, Friend leukemia integration 1 transcription factor, CD117 (c-kit), phospho-S6 (pS6), PDGF receptor-β, VEGF, and phospho-mTOR. Both intensity and extent of staining were scored. Multiplying these scores for each core yielded total staining H-scores. Human herpes virus-8 was positive in 87% and Friend leukemia integration 1 transcription factor in 95.7% of cases. Most were also VEGF+ (97.6%), pS6+ (95.7%), CD117+ (92.5%), and PDGFRB+ (87.4%). Approximately half (55.6%) were phospho-mTOR+. There was no significant difference in staining among patients with low (<500 cells/mm3) or preserved CD4 T-cell counts. Immunohistochemistry confirms upregulation of the mTOR, PDGF, VEGF, and c-kit pathways in a large cohort of KS samples. Of proteins tested, pS6, downstream of mTOR, demonstrated the highest proportion of strong positivity (67.1%). These results support the possibility of using targeted inhibitors in KS. Overexpression was independent of CD4 count, suggesting that even patients with low counts may be targeted therapy candidates.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Human Pathology - Volume 65, July 2017, Pages 157-165
نویسندگان
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