Stem cell-associated transcription factors in non-functioning pituitary neuroendocrine tumours

Authors

  • Kristin Astrid Øystese Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway
  • Nicoleta Cristina Olarescu Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
  • Cecilia Lindskog Cancer precision medicine, Department of Immunology, Genetics and Pathology; Uppsala University, Uppsala, Sweden
  • Fabjola Xheka Department of Clinical Pathology, Uppsala University Hospital, Uppsala, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Solna, Stockholm, Sweden
  • Jon Berg-Johnsen Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Neurosurgery, Oslo University Hospital, Oslo, Norway
  • Jens Petter Berg Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
  • Jens Bollerslev Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
  • Olivera Casar-Borota Department of Clinical Pathology, Uppsala University Hospital, Uppsala, Sweden; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

DOI:

https://doi.org/10.17879/freeneuropathology-2024-5396

Keywords:

Pituitary neoplasm, Non-functioning pituitary adenoma, Neoplastic stem cells, Stem cells

Abstract

Background: Cells with stem cell features have been described in pituitary neuroendocrine tumours (PitNETs). Transcription factors SOX2 and SOX9 are stem cell-associated markers while the pituitary progenitor marker PROP1 is involved in anterior pituitary development. We characterised the presence of these markers known to be present in the human pituitary in non-functioning (NF) PitNETs.

Methods: We investigated the pituitary transcription factors SOX2, SOX9 and PROP1 by immunohistochemistry (IHC) (N = 125) and RT-qPCR (N = 78) in a retrospective cohort of clinically NF-PitNETs. The markers were scored based on the percentage of immunolabeled cells. IHC staining scores were compared to reintervention rates for the whole cohort, and to expression of FSH, LH or ER in gonadotroph NF-PitNETs.

Results: Most tumours showed no or few cells positive for SOX2, SOX9 and PROP1. More patients with SOX2-negative tumours went through reintervention (40 % vs 19 %, p = 0.03).
SOX2, SOX9 and PROP1 staining correlated positively to each other (SOX2 and SOX9 rs = 0.666, SOX2 and PROP1 rs = 0.704, SOX9 and PROP1 rs = 0.570, and p < 0.001 for all).
In gonadotroph NF-PitNETs, staining for SOX2 and PROP1 was positively associated to FSHβ staining (p < 0.001 for both). Staining for SOX2, SOX9 and PROP1 was positively associated with gene expression of Estrogen Receptor 1 (ESR1) (p < 0.001, p = 0.004 and p < 0.001) and IHC staining for ERα (p = 0.001, p = 0.03 and p = 0.05, respectively).

Conclusion: SOX2, SOX9 and PROP1 were present at low levels in NF-PitNETs. Absence of SOX2 staining was associated with a higher reintervention rate. The stem cell markers correlated positively with markers of gonadotroph differentiation in gonadotroph NF-PitNETs. SOX2 and SOX9 were frequently coexpressed and showed positivity in intratumoural cells with epithelial features, however without coexpression of pituitary transcription factors.

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Published

2024-06-06

How to Cite

Øystese, K. A., Olarescu, N. C., Lindskog, C., Xheka, F., Berg-Johnsen, J., Berg , J. P., Bollerslev, J., & Casar-Borota, O. (2024). Stem cell-associated transcription factors in non-functioning pituitary neuroendocrine tumours. Free Neuropathology, 5, 14. https://doi.org/10.17879/freeneuropathology-2024-5396

Issue

Vol. 5 (2024)

Section

Original Papers

License

Copyright (c) 2024 Kristin Astrid Øystese, Nicoleta Cristina Olarescu, Cecilia Lindskog, Fabjola Xheka, Jon Berg-Johnsen, Jens Petter Berg , Jens Bollerslev, Olivera Casar-Borota

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This work is licensed under a Creative Commons Attribution 4.0 International License.

Papers are published open access under the Creative Commons BY 4.0 license. This license lets others distribute, remix, adapt, and build upon your work, even commercially, as long as they credit you for the original creation. Data included in the article are made available under the CC0 1.0 Public Domain Dedication waiver, unless otherwise stated, meaning that all copyrights are waived.