ArticleInternational journal of dermatology2025
Upregulated NOTCH2 Expression Is Implicated in the Clinical Aggressiveness of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma.
Article in International journal of dermatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundAtypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) represent clinicopathological variants of a spectrum. It is known that AFX and PDS tumors harbor frequent NOTCH1/2 mutations. However, the expression of Notch signaling pathway-associated proteins in both tumor cells has not been studied before.
methodsWe conducted an immunohistochemical study by performing NOTCH1, NOTCH2, NICD, and HES1 staining on the most representative formalin-fixed paraffin-embedded (FFPE) tumor tissues out of sixty-two patients with the first diagnosis of either AFX (n = 33) or PDS (n = 29) in a single tertiary medical center.
resultsTen patients (PDS, n = 9; AFX, n = 1) had disease progression in terms of locoregional relapse, including local recurrence and regional lymph node metastasis, with a median time-to-(first)-recurrence interval of 8 months after a wide local excision. Among all the Notch expression profiles, only the upregulated NOTCH2 expression has a positive correlation with disease progression [odds ratio (OR): 1.02, 95% confidence interval (CI): 1-1.04, p = 0.029]. Furthermore, HES1 is activated through the NOTCH2 signaling pathway (r (60) = 0.27, p = 0.032) rather than NOTCH1, and NOTCH1 does not appear to be functionally active.
conclusionsUpregulated NOTCH2 expression plays a significant role in disease progression, in part through the canonical signaling pathway involving the downstream effector HES1. Targeting NOTCH2 signaling might hold therapeutic promise in patients with disease progression.
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