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.

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

Bioptical Laboratory Ltd Plzen Czech Republic

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

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

Department of Pathology Faculty of Medicine in Plzen Charles University Plzen Czech Republic

Department of Pathology Military University Hospital Prague Prague Czech Republic

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

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