Pituitary tumours without distinct lineage differentiation express stem cell marker SOX2

• Published in: Pituitary Vol. 27; no. 3; pp. 248 - 258
• Main Authors: Lenders, Nèle F., Thompson, Tanya J., Chui, Jeanie, Low, Julia, Inder, Warrick J., Earls, Peter E., McCormack, Ann I.
• Format: Journal Article
• Language: English
• Published: New York Springer US 2024; Springer Nature B.V
• Subjects: Brain cancer; Brain tumors; Cell differentiation; Cell lineage; Endocrinology; Human Physiology; Immunohistochemistry; Medicine; Medicine & Public Health; Nestin; Patients; Pit1 protein; Pituitary; Pituitary gland; Stem cells; Transcription factors; Tumors; Immunohistochemistry; Tumour; Pituitary; RT-PCR
• ISSN: 1386-341X; 1573-7403; 1573-7403
• DOI: 10.1007/s11102-024-01385-0

Context The recent WHO 2022 Classification of pituitary tumours identified a novel group of ‘plurihormonal tumours without distinct lineage differentiation (WDLD)’. By definition, these express multiple combinations of lineage commitment transcription factors, in a monomorphous population of cells. Objectives To determine the expression of stem cell markers (SOX2, Nestin, CD133) within tumours WDLD, immature PIT-1 lineage and acidophil stem cell tumours, compared with committed cell lineage tumours. Methods Retrospective evaluation of surgically resected pituitary tumours from St Vincent’s Hospital, Sydney. Patients were selected to cover a range of tumour 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 WDLD and those with classically “mature” types. Results On immunohistochemistry, SOX2 was positive in a higher proportion of tumours WDLD compared with those meeting WHO lineage criteria, 7/10 v 10/42 (70 v 23.4%, p  = 0.005). CD133 was positive in 2/10 tumours WDLD 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 WDLD. Conclusions Our study is the first to biologically characterise pituitary tumours WDLD. We demonstrate that these tumours 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.