Oral Presentation ESA-SRB 2023 in conjunction with ENSA

Pituitary Neuroendocrine Tumours without distinct lineage differentiation express stem cell marker SOX2 (#130)

Nele F Lenders 1 2 3 , Tanya Thompson 1 3 , Jeanie Chui 4 , Julia Lowe 4 , Warrick J Inder 5 6 , Peter E Earls 4 , Ann I McCormack 1 2 3
  1. Department of Endocrinology, St Vincent’s Hospital, Sydney, NSW, Australia.
  2. St Vincent’s Clinical School, University of New South Wales, Sydney, NSW, Australia.
  3. Garvan Institute of Medical Research, Sydney, NSW, Australia.
  4. Department of Anatomical Pathology and Cytopathology, St Vincent's Pathology, Sydney, NSW, Australia
  5. University of Queensland, Brisbane, QLD
  6. Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, QLD, Australia

Context:  The recent WHO 2022 Classification of pituitary neuroendocrine tumours (PitNETs) identified a novel group of tumours, ‘plurihormonal tumours without distinct lineage differentiation’. By definition, these express multiple combinations of lineage commitment transcription factors, in a monomorphous population of cells. The biology of these tumours has not yet been well characterised.

Objectives: To determine the expression of stem cell markers (SOX2, Nestin, CD133) within PitNETs without distinct lineage differentiation, immature PIT-1 lineage and acidophil stem cell tumours, compared with committed cell lineage tumours.

Methods: Retrospective evaluation of surgically resected PitNETs from St Vincent’s Hospital, Sydney. Patients were selected to cover a range of PitNET types, based on transcription factor and hormone immunohistochemistry. Clinical data was collected from patient files. Radiology reports were reviewed for size and invasion.  Samples were analysed by immunohistochemistry and RT-qPCR for SF-1, PIT-1, T-PIT, SOX2, Nestin and CD133. Stem cell markers were compared between tumours without distinct lineage differentiation and those with classically “mature” types.

Results: On immunohistochemistry, SOX2 was positive in a higher proportion of tumours without distinct lineage differentiation compared with those meeting WHO lineage criteria, 7/10 (70%) v 10/42 (23.4%), P=0.005. CD133 was positive in 2/10 tumours without distinct lineage differentiation but 0/41 meeting lineage criteria, P=0.003. On RT-qPCR, there was no significant difference in relative expression of stem cell markers (SOX2, CD133, Nestin) between tumours with and without distinct cell lineage.

Conclusions: Our study is the first to biologically characterise plurihormonal tumours without distinct lineage differentiation. PitNETs without distinct lineage differentiation exhibit a higher expression of the stem cell marker SOX2 compared with other lineage-differentiated tumours, suggesting possible involvement of stem cells in their development. By expanding our knowledge of pituitary tumourigenesis, we aim to develop scope for targeted therapies that may be used to treat tumours in early stages.