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

In Nigeria, patients with pituitary neuroendocrine tumours (PitNETs) commonly present late with complications. Early identification of aggressive PitNETs could improve outcomes.

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.

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).

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).

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.

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.