Oral Presentation Australian and New Zealand Pituitary Alliance 2025

Chromosomal instability is frequent among lactotroph and corticotroph pituitary tumours and may be important in predicting aggressive behaviour (123834)

Ann McCormack 1 2 3 , Lydia Lamb 2 , Nele Lenders 1 2 3 , Tanya Thompson 2 , Hao-Wen Sim 1 , Ngaire Jose 4 , Dorothy Hung 4 , Julia Low 3 5 , Peter Earls 5 , Dale Wright 4
  1. St Vincent's Hospital, Darlinghurst, NSW, Australia
  2. Hormones and Cancer Group, Garvan Institute of Medical Research, Sydney, Australia
  3. St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
  4. Sydney Genome Diagnostics, Children's Hospital Westmead, Sydney, NSW, Australia
  5. Department of Anatomical Pathology and Cytopathology, St Vincent's Pathology, Sydney, NSW, Aus

Background:
Pituitary neuroendocrine tumors (PitNETs) display a broad spectrum of clinical behaviour, with some exhibiting aggressive growth despite standard therapies. Chromosomal instability resulting in extensive chromosomal alterations, has been recognised in a subset of pituitary tumours (1). Recent studies highlight chromosomal instability as a potential marker of aggressive behaviour, particularly among lactotroph and corticotroph tumours​ (2,3)​​.

Aim:

To investigate chromosomal instability among operated PitNETs.

Methods:
Patients undergoing pituitary surgery at St Vincent’s Hospital between January and April 2025 were included in a pilot study. Copy number variation (CNV) was assessed using SNP microarray performed using the Illumina Global-Diversity-Array Cyto v3 platform with analysis using VIA (v7) software (Bionano). Chromosomal patterns were categorised into one of 4 groups (A. no alterations, B. loss of heterozygosity (LOH) or chromosomal losses, C. chromosomal gains, D. mixed). In addition, fraction of genome altered (FGA) and fraction of LOH (FLOH) were calculated. Highly-altered tumours were classified as those with FGA 20% and/or FLOH 11%.

Results:
12 tumour samples (58% female, 83% macroadenomas) were analysed (7 gonadotroph, 2 corticotroph, 2 lactotroph, 1 mature plurihormonal Pit1). All except one were first surgeries. There were no proliferative tumours (Ki67 ³ 3%), 4 tumours were invasive (clinicopathological grade 2a). 3/12 tumours (25%) demonstrated highly-altered genomes with FGA 19.4-73.3% and FLOH 4.4-14%. These compromised both male lactotroph tumours (the only 2 tumours of high-risk histological subtype) and 1 of the corticotroph tumours (female). 2 tumours exhibited pattern C, 1 pattern D and 9 tumours Pattern A.

Conclusion:
This pilot study confirms widespread chromosomal alterations in a significant subset of PitNETs, particularly lactotroph and corticotroph tumours. These subtypes predominate among aggressive pituitary tumours. A larger study is ongoing to determine whether CNV analysis may contribute to prognostication among PitNETs. 

 

  1. (1) Neou M, Villa C, Armignacco R, et al. 2020. Pangenomic classification of pituitary neuroendocrine tumors. Cancer Cell. 37: 123–134
  2. (2) Jentus M, Bakker L, Verstegen M, et al. 2024. Chromosomal alteration patterns in PitNETs: massive losses in aggressive tumors. Endocrine-Related Cancer. 32. e240070
  3. (3) Lin A, Rudneva V, Richards A, et al. 2024. Genome-wide loss of heterozygosity predicts aggressive, treatment-refractory behavior in pituitary neuroendocrine tumors. Acta Neuropathologica. 147(1):85.