Digital assessment of rare pituitary neuroendocrine tumour subtypes reveals increased expression of cytotoxic T-Lymphocyte associated protein 4

Robinson Ann M; Amelia Sheerin; Mary Mallon; Michael Upritchard; Richard Murray; Aoife McArdle; Fionn Corr; Steven J Hunter; Marta Korbonits; Jacqueline A James; Stephanie G Craig; Paul B Loughrey

doi:10.1530/endoabs.115.P1

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Endocrine Abstracts (2026) 115 P1 | DOI: 10.1530/endoabs.115.P1

IES2025 Research, Audit and Quality Improvement Projects Physical Posters (55 abstracts)

Digital assessment of rare pituitary neuroendocrine tumour subtypes reveals increased expression of cytotoxic T-Lymphocyte associated protein 4

Ann M Robinson ¹ , Amelia Sheerin ¹ , Mary Mallon ¹ , Michael Upritchard ¹ , Richard Murray ¹ , Aoife McArdle ¹ , Fionn Corr ¹ , Steven J Hunter ² , Márta Korbonits ³ , Jacqueline A James ^1,2 , Stephanie G Craig ² & Paul B Loughrey ^1,2

Author affiliations

¹Queen’s University Belfast, Belfast, United Kingdom ²Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast, United Kingdom; ³Queen Mary University of London, London, United Kingdom

Pituitary neuroendocrine tumours (PitNETs) are common intracranial neoplasms, with rare subtypes causing growth hormone (GH) excess and hypercortisolaemia. The immune microenvironment of such tumours remains incompletely characterised, and with the description of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor-induced hypophysitis, interest in the potential roles of CTLA-4 in the pituitary has grown. The aim of this work was to investigate the expression of CTLA-4 in PitNETs causing GH excess (n = 74) or hypercortisolaemia (n = 27) and compare it to the expression of CTLA-4 in normal pituitary tissue (n = 4). PitNET tissue samples and normal pituitary resected adjacent to Rathke cleft cysts were stained with a bespoke multiplex biomarker panel using the Leica Bond RX then scanned with the Phenoimager HT. CTLA-4 expression was assessed using QuPath image analysis software. In brief, the subcellular detection function was used calculate fluorescent pixel areas in spots and clusters to quantify CTLA-4 expression. CTLA-4 expression was significantly different across tumour subtypes and normal pituitary tissue (P < 0.001). Expression was higher in corticotrophinomas compared to PitNETs causing GH excess (P = 0.001) and normal pituitary (P = 0.002). It was also higher in PitNETs causing GH excess compared to normal pituitary (P = 0.004). These findings indicate that CTLA-4 is upregulated in PitNETs, particularly corticotrophinomas. With recently published guidelines now considering immunotherapy as a therapeutic modality for aggressive PitNETs, quantification of CTLA-4 and functional studies of its role in PitNETs may become increasingly important.