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  3. Differential Neurod1, Ascl1, And Pou2f3 Expression Defines Molecular Subsets Of Bladder Small Cell/neuroendocrine Carcinoma With Prognostic Implications.
  1. Home
  3. Differential Neurod1, Ascl1, And Pou2f3 Expression Defines Molecular Subsets Of Bladder Small Cell/neuroendocrine Carcinoma With Prognostic Implications.

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Differential NEUROD1, ASCL1, and POU2F3 Expression Defines Molecular Subsets of Bladder Small Cell/Neuroendocrine

Dilara Akbulut1, Karissa Whiting2, Min-Yuen Teo3

  • 1Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
|July 4, 2024

View abstract on PubMed

Summary
This summary is machine-generated.
Keywords:
ASCL1DLL3NEUROD1PLCG2POU2F3small cell carcinoma

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This study identifies five molecular subtypes of bladder neuroendocrine carcinoma (NEC) based on key markers. POU2F3 and PLCG2 expression correlates with poorer survival, while DLL3 is a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Pathology
  • Cancer Genomics

Background:

  • Small cell lung carcinoma (SCLC) is classified by transcriptional regulators (NEUROD1, ASCL1, POU2F3, YAP1) and DLL3.
  • PLCG2 identifies a poor-prognosis subpopulation in lung SCLC with stem cell-like and prometastatic features.
  • Bladder neuroendocrine carcinoma (NEC) classification and therapeutic targets require further elucidation.

Purpose of the Study:

  • To molecularly classify bladder neuroendocrine carcinoma (NEC) using novel and traditional neuroendocrine markers.
  • To investigate the association of these markers with patient outcomes, including overall survival (OS) and recurrence-free survival (RFS).
  • To evaluate DLL3 as a potential therapeutic target in bladder NEC.

Main Methods:

  • Analysis of 103 small cell NEC (SMC) and 19 large cell NEC (LCNEC) samples using tissue microarrays.
  • Assessment of coexpression patterns of ASCL1, NEUROD1, POU2F3, YAP1, PLCG2, and DLL3.
  • Integration of marker expression with clinical data, including OS, RFS, and chemotherapy response.

    • Main Results:

    • Five distinct molecular subtypes of bladder SMC were identified based on ASCL1, NEUROD1, and POU2F3 expression.
    • POU2F3+ tumors were mutually exclusive with ASCL1/NEUROD1 expression and showed lower traditional neuroendocrine marker expression.
    • PLCG2 expression, correlated with POU2F3, was found in 32% of tumors and associated with shorter RFS and OS in non-metastatic patients.
    • DLL3 was highly expressed in both SMC (82%) and LCNEC (85%), while YAP1 was enriched in non-neuroendocrine components.
    • No significant association was found between marker expression and metastasis status or chemotherapy response.

    Conclusions:

    • Bladder NEC can be molecularly subtyped using ASCL1, NEUROD1, and POU2F3.
    • POU2F3-expressing tumors represent a distinct subset of bladder NEC with reduced traditional neuroendocrine markers.
    • PLCG2 and POU2F3 expression are linked to unfavorable survival outcomes.
    • High DLL3 expression in both SMC and LCNEC suggests its potential as a therapeutic target.