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Stem Cell Transcription Factor Sox2 Is Expressed in a Subset of Folliculo-stellate Cells of Growth Hormone–Producing Pituitary Neuroendocrine Tumours and Its Expression Shows No Association with Tumour Size or IGF1 Levels: a Clinicopathological Study of 109 Cases

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Abstract

Sox2 is one of the transcription factors responsible for the maintenance of stem cell phenotype. It has been implicated as a marker of stem cells in normal pituitaries and pituitary neuroendocrine tumours. To explore the clinical significance of Sox2 expression in histological sections, we performed immunohistochemical detection of Sox2 in 113 pituitary neuroendocrine tumours from 109 patients with acromegaly. In 11 tumours, we performed double immunostaining for Sox2, annexin A1 and S100 protein. Tumours were characterised using the WHO classification system. Proliferative activity and invasion were assessed. The amount of immunoreactive cells was evaluated and correlated with tumour size and biochemical features (levels of IGF1, GH, prolactin, βTSH). Sox2+ cells were identified in 35/38 normal pituitaries adjacent to the tumours. In 36 tumours (33%), ≥ 1% of the cells expressed Sox2, in 24 cases (22%), Sox2+ cells comprised < 1% and 49 cases (45%) were negative. We found no significant differences between Sox2+ and Sox2− groups with respect to the age, initial levels of GH, IGF1, prolactin, βTSH, tumour size, invasion, proliferative activity or histological features. We observed a positive correlation between Sox2+ cell count and βTSH immunoreactive cells (r = 0.459, p < 0.001) that was further verified by multivariate analysis. Using double stain, the majority of Sox2+ cells coexpressed annexin A1 (average 89%) and S100 protein (average 76.2%) and showed morphological features of folliculo-stellate cells. Sox2+ cells are thus commonly present in growth hormone–producing tumours and normal pituitaries, and their amount does not have any prognostic significance. Most of these cells represent a subpopulation of folliculo-stellate cells, pointing out to their role as a possible stem cell population.

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Acknowledgements

We would like to thank prof. MUDr. Ales Ryska, Ph.D., for reading the manuscript and for his valuable comments and RNDr. Eva Cermakova for performing advanced statistical analysis of the data. This study was supported by the Ministry of Health, Czech Republic, project No. NV19-01-00435. These centres and investigators were involved in the RESET registry: General University Hospital in Prague: prof. MUDr. Josef Marek, CSc., Prof. MUDr. Vaclav Hana, CSc; St. Anne’s University Hospital in Brno: MUDr. Vera Olsovska, Ph.D., MUDr. Helena Siprova, MUDr. Dalibor Zeman; University Hospital Hradec Králové: prof. MUDr. Jan Čáp, CSc., Assoc. MUDr. Filip Gabalec; University Hospital Pilsen: MUDr. Michal Krcma, Ph.D., MUDr. Eva Dvořáková; University Hospital Brno: MUDr. Karel Starý; University Hospital Bratislava: MUDr. Ludmila Trejbalová, Assoc. MUDr. Jan Podoba, CSc.; University Hospital Bratislava, Department of Neurosurgery: prof. MUDr. Juraj Steno, CSc; National Institute of Endocrinology and Diabetes, Ľubochňa: MUDr. Peter Vaňuga, Ph.D. Peter Kentoš. L. Pasteur University Hospital in Košice: prof. MUDr. Ivica Lazurova, CSc., MUDr. Hedviga Wagner, Ph.D.

Funding

This study was supported by the Ministry of Health CZ project No. NV19-01-00435 (MH CZ NV19-01-00435). All rights reserved.

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Authors and Affiliations

  1. The Fingerland Department of Pathology, University Hospital and Faculty of Medicine Hradec Kralove, Charles University, Sokolska 581, 500 05, Hradec Kralove, Czech Republic

    Jiri Soukup & Helena Hornychová

  2. Department of Neurosurgery, University Hospital and Faculty of Medicine Hradec Kralove, Charles University, Sokolska 581, 500 05, Hradec Kralove, Czech Republic

    Tomáš Česák

  3. Department of Pathology, Faculty of Medicine in Plzen, Charles University, Plzen, Czech Republic

    Květoslava Michalová

  4. Bioptical Laboratory, Ltd., Plzen, Czech Republic

    Květoslava Michalová

  5. Department of Pathology, Military University Hospital Prague, Prague, Czech Republic

    Ľudmila Michnová

  6. Department of Neurosurgery and Neurooncology, 1st Medical Faculty, Charles University, Military University Hospital Prague, Prague, Czech Republic

    David Netuka

  7. 4th Department of Internal Medicine, University Hospital and Faculty of Medicine Hradec Kralove, Charles University, Sokolska 581, 500 05, Hradec Kralove, Czech Republic

    Jan Čáp & Filip Gabalec

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  1. Jiri Soukup
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  8. Filip Gabalec
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Correspondence to Jiri Soukup.

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Conflict of Interest

Jiri Soukup and Filip Gabalec received research grant from Company Pfizer in the past; this had no impact on design, evaluation or interpretation of the current study. The remaining authors declare that they have no conflict of interest.

Ethics Approval

The study had a consent of the ethical committee of the first author’s institution, where the experimental part was performed. The research was conducted in accordance with the 1964 Helsinki Declaration.

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All patients included in the RESET database had signed an informed consent agreeing with a future research use of the tissue and clinical data.

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Soukup, J., Česák, T., Hornychová, H. et al. Stem Cell Transcription Factor Sox2 Is Expressed in a Subset of Folliculo-stellate Cells of Growth Hormone–Producing Pituitary Neuroendocrine Tumours and Its Expression Shows No Association with Tumour Size or IGF1 Levels: a Clinicopathological Study of 109 Cases. Endocr Pathol 31, 337–347 (2020). https://doi.org/10.1007/s12022-020-09634-1

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