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

Abstract

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. (Endokrynol Pol 2017; 68 (4): 380-389)

Stratifying nonfunctional pituitary adenomas into two groups distinguished by macrophage subtypes

“…S100A9 is a member of the S100 family of calcium-binding proteins that may serve as an inhibitor of casein kinase. S100 proteins have been shown to be expressed in pituitary adenomas in a manner that correlates with VEGF and EGFR expression [31]. Furthermore, while S100 proteins have not been directly linked to invasion in pituitary adenomas, the S100A8 and S100A9 proteins have been shown to mediate TAM-induced metastases in colon and lung cancer cell lines [32] and their heterodimer protein, calprotectin, has been found to induce members of the NF-kB and p38 pathways in macrophages, stimulating increased release of pro-inflammatory cytokines [33].…”

Hedgehog signaling in endocrine and folliculo-stellate cells of the adult pituitary

“…However, our findings could be of importance for several pituitary adenoma subtypes, in which HH signaling is activated . It is possible that Hh signaling activation in tumor-associated FSC, which are found in large numbers at the periphery of adenomas and other pituitary lesions (Nishioka et al, 1991, Cimpean et al, 2017, Voit et al, 1999, Horvath and Kovacs, 2002) support hormone production from tumor cells. This opens the intriguing possibility that hormone production of tumor cells depends on Hh signaling activity in adjacent FSC, which thus might represent a target for future therapeutic intervention.…”

Zmiany torbielowate okolicy siodłowo-nadsiodłowej — diagnostyka i leczenie

“…Cells related to neoplasmatic changes, co-expressing cytokeratins, GFAP and S-100, have been found in Rathke's cleft cyst. The occurrence of cells with a similar phenotype in pituitary adenomas seems to be associated with invasiveness and recurrence of tumours [16].…”