Vol 68, No 4 (2017)
Original paper
Published online: 2017-05-26

open access

Page views 2133
Article views/downloads 1727
Get Citation

Connect on Social Media

Connect on Social Media

The “game” of glial fibrillary acidic and S100 proteins in pituitary adenomas: two players or several?

Anca Maria Cimpean1, Amalia Raluca Ceausu2, Ana Corlan3, Eugen Melnic4, Andreea Adriana Jitariu2, Marius Raica2
Pubmed: 28660986
Endokrynol Pol 2017;68(4):380-389.


Introduction: S100 protein and GFAP expression in pituitary adenomas tumour cells is not well known; few correlations with other prognostic or therapeutic factors have previously been reported in pituitary adenomas. We aim to elucidate their involvement in the pathogenesis of pituitary adenomas and to establish the correlation of their expression with different growth factors and growth factor receptors known to have a prognostic and/or therapeutic role.

Material and methods: Sixty-one cases of pituitary adenomas were immunohistochemically assessed for the expression of GFAP and S100 protein in both tumour cells and FS cells, in close relationship with hormone profile, and correlated with vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expression, previously studied by our team.

Results: GFAP and S100 protein were expressed both in tumour cells and FS cells. Differences between morphology, distribution, and density of GFAP+ FS cells and S100+ FS cells were observed according to the hormone profile of pituitary adenomas. GFAP and S100 protein expression in tumour cells was significantly related to hormone profile of pituitary adenomas and also with VEGF and EGFR expression.

Conclusions: GFAP and S100 protein expressions in tumour cells from pituitary adenomas are influenced by hormone profile. Our re­sults support the presence of two molecular subtypes of FS cells GFAP+/VEGF+/S100 respectively and another one that is GFAP-/S100+/EGFR+ simultaneously with the classical variant GFAP+/S100+. It is possible that S100+/EGFR+ pituitary adenomas represent a group of pituitary adenomas with an aggressive behaviour and a high ability of invasion and recurrence.


  1. Kasper M, Kasper M, Kern F, et al. Immunohistochemical studies on human pituitary gland and adenomas. J Hirnforsch. 1991; 32(6): 725–734.
  2. Marin F, Boya J, Lopez-Carbonell A, et al. Immunohistochemical localization of intermediate filament and S-100 proteins in several non-endocrine cells of the human pituitary gland. Arch Histol Cytol. 1989; 52(3): 241–248.
  3. Wu JL, Qiao JY, Duan QH. Significance of TNF-α and IL-6 expression in invasive pituitary adenomas. Genet Mol Res. 2016; 15(1).
  4. Cykowski MD, Takei H, Baskin DS, et al. Epithelial and organ-related marker expression in pituitary adenomas. Neuropathology. 2016; 36(4): 354–364.
  5. Phillips JJ, Misra A, Feuerstein BG, et al. Pituicytoma: characterization of a unique neoplasm by histology, immunohistochemistry, ultrastructure, and array-based comparative genomic hybridization. Arch Pathol Lab Med. 2010; 134(7): 1063–1069.
  6. Zhang F, Chen J, You C. Pituicytoma: case report and review of the literature. Neurol India. 2010; 58(5): 799–801.
  7. Kwon MiJ, Suh YL. Pituicytoma with unusual histological features. Pathol Int. 2011; 61(10): 598–602.
  8. Ida CM, Yan X, Jentoft ME, et al. Pituicytoma with gelsolin amyloid deposition. Endocr Pathol. 2013; 24(3): 149–155.
  9. Giometto B, Miotto D, Botteri M, et al. Folliculo-stellate cells of human pituitary adenomas: immunohistochemical study of the monocyte/macrophage phenotype expression. Neuroendocrinology. 1997; 65(1): 47–52.
  10. Jovanović I, Ugrenović S, Ljubomirović M, et al. Folliculo-stellate cells - potential mediators of the inflammaging-induced hyperactivity of the hypothalamic-pituitary-adrenal axis in healthy elderly individuals. Med Hypotheses. 2014; 83(4): 501–505.
  11. Sakuma E, Wada I, Soji T, et al. The changes of gap junctions between pituitary folliculo-stellate cells during the postnatal development of Zucker fatty and lean rats. Microsc Res Tech. 2014; 77(1): 31–36.
  12. Kapitonova MIu, Ullah M, Kuznetsov SL, et al. [Age-related changes of the pituitary folliculo-stellate cells in rats in chronic stress]. Vestn Ross Akad Med Nauk. 2013(11): 98–102.
  13. Vajtai I, Beck J, Kappeler A, et al. Spindle cell oncocytoma of the pituitary gland with follicle-like component: organotypic differentiation to support its origin from folliculo-stellate cells. Acta Neuropathol. 2011; 122(2): 253–258.
  14. Borota OC, Scheithauer BW, Fougner SL, et al. Spindle cell oncocytoma of the adenohypophysis: report of a case with marked cellular atypia and recurrence despite adjuvant treatment. Clin Neuropathol. 2009; 28(2): 91–95.
  15. Alexandrescu S, Brown RE, Tandon N, et al. Neuron precursor features of spindle cell oncocytoma of adenohypophysis. Ann Clin Lab Sci. 2012; 42(2): 123–129.
  16. Yoshimoto T, Takahashi-Fujigasaki J, Inoshita N, et al. TTF-1-positive oncocytic sellar tumor with follicle formation/ependymal differentiation: non-adenomatous tumor capable of two different interpretations as a pituicytoma or a spindle cell oncocytoma. Brain Tumor Pathol. 2015; 32(3): 221–227.
  17. Burghaus S, Hölsken A, Buchfelder M, et al. A tumor-specific cellular environment at the brain invasion border of adamantinomatous craniopharyngiomas. Virchows Arch. 2010; 456(3): 287–300.
  18. Vinores SA. Demonstration of glial fibrillary acidic (GFA) protein by electron immunocytochemistry in the granular cells of a choristoma of the neurohypophysis. Histochemistry. 1991; 96(3): 265–269.
  19. Tateno T, Nakano-Tateno T, Ezzat S, et al. NG2 targets tumorigenic Rb inactivation in Pit1-lineage pituitary cells. Endocr Relat Cancer. 2016; 23(5): 445–456.
  20. de Herder WW. Molecular Imaging of Pituitary Pathology. Front Horm Res. 2016; 45: 133–141.
  21. Inoue K, Couch EF, Takano K, et al. The structure and function of folliculo-stellate cells in the anterior pituitary gland. Arch Histol Cytol. 1999; 62(3): 205–218.
  22. Devnath S, Inoue K. An insight to pituitary folliculo-stellate cells. J Neuroendocrinol. 2008; 20(6): 687–691.
  23. Horvath E, Kovacs K. Folliculo-stellate cells of the human pituitary: a type of adult stem cell? Ultrastruct Pathol. 2002; 26(4): 219–228.
  24. Min HS, Lee SJ, Kim SK, et al. Pituitary adenoma with rich folliculo-stellate cells and mucin-producing epithelia arising in a 2-year-old girl. Pathol Int. 2007; 57(9): 600–605.
  25. Fu Q, Gremeaux L, Luque RM, et al. The adult pituitary shows stem/progenitor cell activation in response to injury and is capable of regeneration. Endocrinology. 2012; 153(7): 3224–3235.
  26. Westerman BA, Blom M, Tanger E, et al. GFAP-Cre-mediated transgenic activation of Bmi1 results in pituitary tumors. PLoS One. 2012; 7(5): e35943.
  27. Gospodarowicz D, Lau K. Pituitary follicular cells secrete both vascular endothelial growth factor and follistatin. Biochemical and Biophysical Research Communications. 1989; 165(1): 292–298.
  28. Luo X, Xie H, Long X, et al. EGFRvIII mediates hepatocellular carcinoma cell invasion by promoting S100 calcium binding protein A11 expression. PLoS One. 2013; 8(12): e83332.
  29. Johnson H, Del Rosario AM, Bryson BD, et al. Molecular characterization of EGFR and EGFRvIII signaling networks in human glioblastoma tumor xenografts. Mol Cell Proteomics. 2012; 11(12): 1724–1740.
  30. Weissinger SE, Keil P, Silvers DN, et al. A diagnostic algorithm to distinguish desmoplastic from spindle cell melanoma. Mod Pathol. 2014; 27(4): 524–534.