INSM1 (INSM Transcriptional Repressor 1)

INSM1 overexpression in SH-SY-5Y cells upregulated neuroendocrine and thyroid hormone-related genes (CHGA, CHGB, DDC, NCAM1, DIO3, TH), while suppressing genes involved in cell cycle (RRM, CDC25A), methionine metabolism (AHCY, MAT2A), transcriptional regulation (MYBL2, EZH2), and oncogenic signaling (ALK, LINC011667). These findings suggest that INSM1 promotes NB aggressiveness by sustaining a neuroendocrine progenitor-like phenotype through metabolic-epigenetic coupling.

The ASCL1/INSM1-NLR composite biomarker stratifies survival outcomes for unresectable SCLC patients treated with first-line chemoimmunotherapy with or without radiotherapy. Prospective multicenter validation is required.

This case report highlights a potential diagnostic pitfall, as INSM1 expression may be misleading in EBV-associated carcinomas lacking true neuroendocrine differentiation. Integration of morphology, immunoprofile, and EBV status is essential to avoid misclassification.

INSM1 is highly expressed in human glioblastoma tumors and, during cortical development, in intermediate progenitor cells, which give rise to neurons. Remarkably, INSM1 knockdown in triple mutant NSCs and primary glioblastoma cells disrupts oncogenic gene expression and function and inhibits the in vivo tumorigenicity of triple mutant NSCs, highlighting the functional importance of an intermediate progenitor cell-like cell state in glioblastoma pathogenesis.

Among all comparisons, only SSTR2A expression significantly differed between DTs and other tumours. In conclusion, Ki-67 and INSM1 identify patients with more aggressive MTC, while SSTR2A defines a favourable subgroup with complete remission.

In this limited series, mutational signature analysis revealed evidence of SBS87 as the predominant single-base substitution COSMIC signature. Our work expands the possible diagnostic antigen expression of thoracic SMARCA4-dUT, contributes to the emerging reports on patients with variant disease presentation, and highlights the need for large-scale genomic studies to determine additional mechanisms of the initiation of carcinogenesis.

In summary, simultaneous CD5 and INSM1 expression may serve as a distinct feature for parotid CASTLE, facilitating differential diagnosis in salivary gland pathology. In addition, EBER ISH remains essential to exclude LEC.

INSM1 nuclear positivity in gastric neoplasms should be interpreted with caution. INSM1 should not be used as a stand-alone marker for determining neuroendocrine differentiation in gastric tumors. Histologic evaluation with concurrent use of traditional neuroendocrine markers is warranted to accurately demonstrate neuroendocrine differentiation and minimize false positivity and false negativity.

Instead, INSM1 collaborates with CTCF to target genome loci having the GGGG-contained element and regulate the expression of adjacent genes. This study defines a functional mode of INSM1 by cooperating with diverse DNA-binding proteins for targeting specific genome loci in transcription regulation, and provides structural information for designing INSM1-related therapeutic drugs and diagnostic probes.

SYP-positive and CgA-negative phenotypes may characterize neuroendocrine differentiation in ameloblastoma. Although the underlying molecular mechanism remains unclear, CLU expression may be associated with neuroendocrine differentiation.

Although the INSM1 staining is cytoplasmic in RBCs (lacking nuclei) and nucleated erythroid precursors, the morphological features can mimic positive nuclear staining of neuroendocrine neoplasms. Particularly in small biopsy samples, which often contain background RBCs, positive INSM1 staining should be reviewed with caution to avoid misdiagnosis of neuroendocrine differentiation.