Adamantinoma-like Ewing sarcoma(ALES)is a rare variant of Ewing sarcoma that predominantly occurs in the head and neck region,characterized by epithelial differentiation and overlapping morphology with other small rou...Adamantinoma-like Ewing sarcoma(ALES)is a rare variant of Ewing sarcoma that predominantly occurs in the head and neck region,characterized by epithelial differentiation and overlapping morphology with other small round cell tumors.We present three cases of head and neck ALES(two in the parotid gland and one in the nasal cavity)in patients aged 23-42 years.Histologically,the tumors exhibited a spectrum of features,including small round blue cells and basaloid squamous morphologies.Immunohistochemically,the tumor cells variably expressed CKpan,p63,CD99,NKX2.2,FLI1,CD56,and Syn.The Ki-67 proliferation index ranged widely from 15%to 90%.Notably,one case initially misdiagnosed as squamous cell carcinoma harbored a canonical EWSR1::FLI1 fusion.Crucially,we report the first case of ALES had a negative EWSR1 rearrangement but a somatic NF1 mutation,expanding the molecular spectrum of this entity.Our findings underscore the diagnostic challenge of ALES and highlight the necessity of comprehensive molecular profiling,including next-generation sequencing,for accurate diagnosis and the identification of potential therapeutic targets,particularly in genetically atypical cases.展开更多
Ewing’s sarcoma is a pediatric tumor that mainly occurs in soft tissues and bones. Malignant characteristics of Ewing’s sarcoma are correlated with expression of EWS oncogene. We achieved knockdown of EWS expression...Ewing’s sarcoma is a pediatric tumor that mainly occurs in soft tissues and bones. Malignant characteristics of Ewing’s sarcoma are correlated with expression of EWS oncogene. We achieved knockdown of EWS expression using a plasmid vector encoding EWS short hairpin RNA (shRNA) to increase anti-tumor mechanisms of taxifolin (TFL), a new flavonoid, in human Ewing’s sarcoma cells in culture and animal models. Immunofluorescence microscopy and flow cytometric analysis showed high expression of EWS in human Ewing’s sarcoma SK-N-MC and RD-ES cell lines. EWS shRNA plus TFL inhibited 80% cell viability and caused the highest decreases in EWS expression at mRNA and protein levels in both cell lines. Knockdown of EWS expression induced morphological features of differentiation. EWS shRNA plus TFL caused more alterations in molecular markers of differentiation than either agent alone. EWS shRNA plus TFL caused the highest decreases in cell migration with inhibition of survival, angiogenic and invasive factors. Knockdown of EWS expression was associated with removal of DNA methylation from p53 promoter, promoting expression of p53, Puma, and Noxa. EWS shRNA plus TFL induced the highest amounts of apoptosis with activation of extrinsic and intrinsic pathways in both cell lines in culture. EWS shRNA plus TFL also inhibited growth of Ewing’s sarcoma tumors in animal models due to inhibition of differentiation inhibitors and angiogenic and invasive factors and also induction of activation of caspase-3 for apoptosis. Collectively, knockdown of EWS expression increased various anti-tumor mechanisms of TFL in human Ewing’s sarcoma in cell culture and animal models.展开更多
文摘Adamantinoma-like Ewing sarcoma(ALES)is a rare variant of Ewing sarcoma that predominantly occurs in the head and neck region,characterized by epithelial differentiation and overlapping morphology with other small round cell tumors.We present three cases of head and neck ALES(two in the parotid gland and one in the nasal cavity)in patients aged 23-42 years.Histologically,the tumors exhibited a spectrum of features,including small round blue cells and basaloid squamous morphologies.Immunohistochemically,the tumor cells variably expressed CKpan,p63,CD99,NKX2.2,FLI1,CD56,and Syn.The Ki-67 proliferation index ranged widely from 15%to 90%.Notably,one case initially misdiagnosed as squamous cell carcinoma harbored a canonical EWSR1::FLI1 fusion.Crucially,we report the first case of ALES had a negative EWSR1 rearrangement but a somatic NF1 mutation,expanding the molecular spectrum of this entity.Our findings underscore the diagnostic challenge of ALES and highlight the necessity of comprehensive molecular profiling,including next-generation sequencing,for accurate diagnosis and the identification of potential therapeutic targets,particularly in genetically atypical cases.
文摘Ewing’s sarcoma is a pediatric tumor that mainly occurs in soft tissues and bones. Malignant characteristics of Ewing’s sarcoma are correlated with expression of EWS oncogene. We achieved knockdown of EWS expression using a plasmid vector encoding EWS short hairpin RNA (shRNA) to increase anti-tumor mechanisms of taxifolin (TFL), a new flavonoid, in human Ewing’s sarcoma cells in culture and animal models. Immunofluorescence microscopy and flow cytometric analysis showed high expression of EWS in human Ewing’s sarcoma SK-N-MC and RD-ES cell lines. EWS shRNA plus TFL inhibited 80% cell viability and caused the highest decreases in EWS expression at mRNA and protein levels in both cell lines. Knockdown of EWS expression induced morphological features of differentiation. EWS shRNA plus TFL caused more alterations in molecular markers of differentiation than either agent alone. EWS shRNA plus TFL caused the highest decreases in cell migration with inhibition of survival, angiogenic and invasive factors. Knockdown of EWS expression was associated with removal of DNA methylation from p53 promoter, promoting expression of p53, Puma, and Noxa. EWS shRNA plus TFL induced the highest amounts of apoptosis with activation of extrinsic and intrinsic pathways in both cell lines in culture. EWS shRNA plus TFL also inhibited growth of Ewing’s sarcoma tumors in animal models due to inhibition of differentiation inhibitors and angiogenic and invasive factors and also induction of activation of caspase-3 for apoptosis. Collectively, knockdown of EWS expression increased various anti-tumor mechanisms of TFL in human Ewing’s sarcoma in cell culture and animal models.
