Collagen-1 content as predictor for recurrence in clinically non-functioning pituitary neuroendocrine tumours (NF-PitNETs)

Ashutosh Rai; Carreira Ana Luis; Thomas Rice; Jack WilliamsWilliams; Kesson Magid; Aiste Mikalauskaite; Shruti Sabnis; Neil Dorward; Joan Grieve; Angelos Kolias; Danyal Khan; Marcus Hani J; Radotra Bishan Dass; Rajesh Chhabra; Pinaki Dutta; Marta Korbonits; Federica Begalli

doi:10.1530/endoabs.109.ER1.3

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Endocrine Abstracts (2025) 109 ER1.3 | DOI: 10.1530/endoabs.109.ER1.3

SFEBES2025 Emerging Researcher and Plenary Orals Clinical Endocrinology Journal Foundation Best Abstract (Clinical) (1 abstracts)

Collagen-1 content as predictor for recurrence in clinically non-functioning pituitary neuroendocrine tumours (NF-PitNETs)

Ashutosh Rai ¹ , Ana Luís Carreira ² , Thomas Rice ³ , Jack WilliamsWilliams ³ , Kesson Magid ³ , Aiste Mikalauskaite ³ , Shruti Sabnis ³ , Neil Dorward ⁴ , Joan Grieve ⁴ , Angelos Kolias ⁴ , Danyal Khan ⁴ , Hani J Marcus ⁴ , Bishan Dass Radotra ⁵ , Rajesh Chhabra ⁵ , Pinaki Dutta ⁵ , Márta Korbonits ³ & Federica Begalli ³

Author affiliations

¹Panjab University, Chandigarh, India. ²Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal. ³William Harvey Research Institute, Queen Mary University of London, London, United Kingdom. ⁴UCL Queen Square Institute of Neurology, London, United Kingdom. ⁵PGIMER, Chandigarh, India

Background: Incomplete resection (30-45%) or recurrence (7-12%) are common features in non-functioning pituitary neuroendocrine tumours (NF-PitNETs). However, we lack predictive biomarkers to help the management of these tumours. Collagen fibres are important structural components of the tumour microenvironment (TME) and have been associated with recurrence and aggressiveness in other cancers. However, their role in NF-PitNETs is unknown.

Method: We performed picrosirius red staining on 6 normal pituitaries (NP) and 73 NF-PitNETs; 49 full slides and 24 as part of tissue microarray, showing homogenous results. Collagens I and III were assessed via polarisation microscope. At least 4 fields of view were analysed from each sample. Additionally, we assessed collagen fibres characteristics: thickness and linearity (number of collagen fibre end points, number of fibre branch points, total length of fibres,), the structural complexity (fibre curvature, alignment, proportion of high-density matrix, ECM fractal dimension), fragmentation (hyphal growth unit), and compactness (matrix gaps, and lacunarity) using the TWOMBLI pipeline.

Results and Discussion: We observed significantly higher percentages of collagen-stained area in recurrent NF-PitNETs compared to non-recurrent and NP (P<0.0001), with collagen I significantly increased, while collagen III significantly decreased in recurrent compared to non-recurrent tumours and NP (P<0.0001). The study of the collagen fibres’ characteristics revealed significant increase in number of fibres, thickness, length, structural complexity, and compactness in recurrent tumours compared to non-recurrent tumours and NP (P<0.0001), while there was a significant decrease in fragmentation in recurrent tumours (P<0.0001). These results show how recurrent NF-PitNETs are characterised by high-density matrix, which is associated with aggressiveness in other cancers. ROC analysis on the percentage of collagen-stained area showed its accuracy as prognostic marker for recurrence in NF-PitNETs (AUC=0.88, P=0.006).

Conclusions: This study highlight TME importance in PitNETs and crucially provides a powerful and easily applicable prognostic marker for recurrence in NF-PitNETs.