Differential expression of cyclin D1 in pituitary neuroendocrine tumours: Relation to aggressive potential

Abstract

Background: In Nigeria, patients with pituitary neuroendocrine tumours (PitNETs) commonly present late with complications. Early identification of aggressive PitNETs could improve outcomes. Objective: This study aimed to determine frequency and degree of cyclin D1 expression in PitNETs and compare levels in aggressive versus non-aggressive tumours and normal pituitary. Methods: Retrospective case–control study (2010–2019) using two tissue microarrays from mitotically active hotspots on paraffin blocks: 70 histologically diagnosed PitNETs and 29 normal pituitary controls. Immunohistochemistry was performed for Ki-67, cyclin D1, anterior pituitary transcription factors, CK MNF116, and hormones. Aggressive PitNETs were classified per 2022 WHO criteria (mitotic rate > 2/10 HPF, Ki-67 ≥ 3% or radiological invasion). Results: Fourteen (20%) PitNETs were classified as aggressive (8 invasive, 6 proliferative). Median age in the aggressive group was 36.5 years with equal gender distribution. The commonest aggressive subtype was PIT-1 lineage lactotroph PitNET (5/14, 35.7%). Moderate–strong nuclear cyclin D1 expression (IRS ≥ 5) occurred in 85.7% of aggressive PitNETs versus 67.9% of non-aggressive tumours and 0% of controls (p < 0.01). Positive predictive value of cyclin D1 for aggressiveness among PitNETs was 24% (12/50 positive cases). Conclusion: Cyclin D1 is significantly overexpressed in aggressive PitNETs compared with non-aggressive tumours and normal pituitary, suggesting its potential as a biomarker for early detection, risk stratification, and therapeutic targeting, especially in resource-limited settings. What the study adds: This study demonstrates marked cyclin D1 overexpression in aggressive PitNETs, supporting its use as a biomarker for early detection, more precise risk stratification, and as a potential therapeutic target in resource-limited environments.