- Design
- Retrospective multi-institutional immunohistochemistry and FISH study
- Population
- 79 bladder small cell carcinomas characterised by IHC
- Primary outcome
- Transcription-factor subtype and therapeutic biomarker expression
- Effect
- ASCL1 41.8%, NEUROD1 25.3%, POU2F3 20.3%; NECTIN4 amplification 21.9%
This multi-institutional Histopathology study, published on 16 September, applied the transcription-factor classification used for small cell lung cancer to 79 bladder small cell carcinomas. Staining for ASCL1, NEUROD1, POU2F3 and YAP1 defined subgroups: ASCL1-driven 41.8%, NEUROD1 25.3%, POU2F3 20.3%, YAP1 6.3%, mixed 5.1% and negative 1.3%.
These fell into two broader groups. High-neuroendocrine tumours (ASCL1, NEUROD1, mixed) had diffuse neuroendocrine markers and more DLL3 and SLFN11. Low-neuroendocrine tumours (POU2F3, YAP1, negative) had weak or absent neuroendocrine markers and more membranous Nectin-4, though Nectin-4 was generally low. NECTIN4 amplification was found in 21.9%.
For the reporting pathologist, the point is that weak or absent chromogranin and synaptophysin do not rule out small cell carcinoma; POU2F3-driven tumours are an established low-neuroendocrine variant in the lung. The therapeutic implications are still research questions.
- Do not exclude small cell carcinoma of the bladder on weak or absent neuroendocrine markers alone.
- Consider POU2F3 staining when morphology suggests small cell carcinoma but markers are weak.
- Note that DLL3 was expressed mainly in high-neuroendocrine tumours.
- Treat target-expression profiles here as research data, not treatment selection criteria.
Why it matters
About a quarter of these tumours had weak or absent neuroendocrine markers, the stains most reports rely on.
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