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1.
Front Biosci (Landmark Ed) ; 29(3): 100, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38538277

RESUMEN

BACKGROUND: As a dedifferentiated tumor, small cell endometrial neuroendocrine tumors (NETs) are rare and frequently diagnosed at an advanced stage with a poor prognosis. Current treatment recommendations are often extrapolated from histologically similar tumors in other sites or based on retrospective studies. The exploration for diagnostic and therapeutic markers in small cell NETs is of great significance. METHODS: In this study, we conducted single-cell RNA sequencing on a specimen obtained from a patient diagnosed with small cell endometrial neuroendocrine carcinoma (SCNEC) based on pathology. We revealed the cell map and intratumoral heterogeneity of the cancer cells through data analysis. Further, we validated the function of ISL LIM Homeobox 1 (ISL1) in vitro in an established neuroendocrine cell line. Finally, we examined the association between ISL1 and tumor staging in small cell lung cancer (SCLC) patient samples. RESULTS: We observed the significant upregulation of ISL1 expression in tumor cells that showed high expression of the neuroepithelial markers. Additionally, in vitro cell function experiments demonstrated that the high ISL1 expression group exhibited markedly higher cell proliferation and migration abilities compared to the low expression group. Finally, we showed that the expression level of ISL1 was correlated with SCLC stages. CONCLUSIONS: ISL1 protein in NETs shows promise as a potential biomarker for diagnosis and treatment.


Asunto(s)
Carcinoma Neuroendocrino , Tumores Neuroendocrinos , Femenino , Humanos , Factores de Transcripción/genética , Estudios Retrospectivos , Análisis de Expresión Génica de una Sola Célula , Proteínas con Homeodominio LIM/genética , Proteínas con Homeodominio LIM/análisis , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/metabolismo , Tumores Neuroendocrinos/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Endometrio/química , Endometrio/metabolismo , Endometrio/patología , Carcinoma Neuroendocrino/diagnóstico , Carcinoma Neuroendocrino/genética , Carcinoma Neuroendocrino/terapia
2.
Pathol Res Pract ; 260: 155469, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39018925

RESUMEN

ISLET-1 (ISL1) is a LIM-homeodomain transcription factor. Selective ISL1 expression is shown in neuroendocrine, non-neuroendocrine, and some soft tissue tumors including desmoplastic small round cell tumor (DSRCT). We assessed the specificity of ISL1 (clone EP283, 1:500, Cell Marque) in 288 soft tissue tumors, which included 17 DSRCTs and other histologic mimics. Positive staining threshold for ISL1 was set to >10 % of neoplastic cell nuclei at moderate intensity. ISL1 IHC was positive in 15/16 (94 %) DSRCTs with 75 % showing diffuse (>50 %) expression. ISL1 was positive in 1/10 (10 %) Ewing sarcomas (EWS), 7/13 (54 %) alveolar rhabdomyosarcoma (RMS), 14/22 (63 %) embryonal RMS, 7/14 (50 %) synovial sarcomas, 15/16 (93 %) neuroblastoma, 1/5 (20 %) Wilms tumor, 2/4 (50 %) olfactory neuroblastoma, and all 9 Merkel cell carcinomas. Other tumors, including all CIC::DUX4 sarcomas, were negative except 3/27 leiomyosarcomas, and 1 each of angiosarcoma, myxoid liposarcomas, inflammatory myofibroblastic tumor, malignant peripheral nerve sheath tumor, tenosynovial giant cell tumor, dedifferentiated LPS, and 1 ectomesenchymoma. In summary, among the soft tissue tumors tested, ISL1 is a highly sensitive but moderately specific marker for DSRCT and may be useful to distinguish from round cell mimics including EWS and CIC::DUX4 sarcomas. The oncogenic role of ISL1 in these tumors warrants further investigation.


Asunto(s)
Biomarcadores de Tumor , Tumor Desmoplásico de Células Pequeñas Redondas , Proteínas con Homeodominio LIM , Neoplasias de los Tejidos Blandos , Factores de Transcripción , Humanos , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Tumor Desmoplásico de Células Pequeñas Redondas/patología , Tumor Desmoplásico de Células Pequeñas Redondas/diagnóstico , Tumor Desmoplásico de Células Pequeñas Redondas/metabolismo , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/metabolismo , Proteínas con Homeodominio LIM/metabolismo , Proteínas con Homeodominio LIM/análisis , Factores de Transcripción/metabolismo , Factores de Transcripción/análisis , Sensibilidad y Especificidad , Inmunohistoquímica
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