Metabolic signature of atypical fibroxanthoma and pleomorphic dermal sarcoma: expression of hypoxia-inducible factor-1α and several of its downstream targets
Metabolic reprogramming mediated by hypoxia-inducible factors play a crucial role in many human cancers. HIF-1α is activated under hypoxic conditions and is considered a key regulator of oxygen homoeostasis during tumor proliferation under hypoxia. Aim of this research was to analyze the immunohisto...
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| Main Authors: | , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2022
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| In: |
Acta dermatovenerologica Croatica
Year: 2022, Volume: 30, Issue: 1, Pages: 25-31 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://hrcak.srce.hr/file/405842
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| Author Notes: | Ferdinand Toberer, Julia K Winkler, Holger A Haenssle, Monika Heinzel-Gutenbrunner, Alexander Enk, Wolfgang Hartschuh, Peter Helmbold, Heinz Kutzner, Doris Helbig |
| Summary: | Metabolic reprogramming mediated by hypoxia-inducible factors play a crucial role in many human cancers. HIF-1α is activated under hypoxic conditions and is considered a key regulator of oxygen homoeostasis during tumor proliferation under hypoxia. Aim of this research was to analyze the immunohistochemical expression of HIF-1α, VEGF-A, Glut-1, MCT4, and CAIX in atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS). 21 paraffin-embedded AFX and 22 PDS were analysed by immunohistochemistry, namely HIF-1α, VEGF-A (referred to as VEGF throughout the manuscript), Glut-1, MCT4, and CAIX. To quantify the protein expression, we considered the percentage of positive tumor cells (0: 0%, 1: up to 1%, 2: 2-10%, 3: 11-50%, 4: >50%) in relation to the staining intensity (0: negative, 1: low, 2: medium, 3: strong). HIF-1α expression (mean ± SD) in AFX (9.33±2.92) was significantly stronger than that in PDS (5.90±4.38; P= 0.007), whereas the expression of VEGF, Glut-1, MCT4, and CAIX did not show differences between AFX and PDS. When comparing all tumors without subgroup stratification, the expression of HIF-1α (P= 0.044) and MCT4 (P= 0.036) was significantly stronger in ulcerated tumors than in tumors without ulceration. Our findings provide the first evidence that HIF-1α-induced metabolic reprogramming may contribute to the pathogenesis of AFX and PDS. HIF-1α expression seems to be higher in AFX than in PDS, and ulcerated tumors show higher expression levels of HIF1α and MCT4 irrespective of the diagnosis. |
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| Item Description: | Gesehen am 21.11.2022 Indexed: 2022-07-28 |
| Physical Description: | Online Resource |