Endocrine Abstracts

Background

Pituitary adenomas are general benign tumors. However, gross invasion at time of operation is observed in up to 35% of pituitary adenomas. The new WHO classification describes pituitary tumor subtypes along with histological markers, such as Ki67 > 3%, that may suggest a potential for aggressive clinical behavior. The expression of EGFR in tumor microenvironment of pituitary adenomas ant its correlation with tumor behavior have been poorly characterized.

Materials and methods

Our study included 92 selected cases (10 normal pituitary glands, 82 pituitary adenomas extracted through transsphenoidal approach). We used standard morphological stain- hematoxylin-eosin to determine the tinctorial classification and the growth pattern of the adenomas. We used the immunohistochemical method to obtain the hormonal profile; we determined the mRNA for the well known growth factors (VEGF, VEGF165b, PDGF A, PDGF B/PDGFR BETA, EG-VEGF) through ISH, respectively the RNA scope technique. We also characterized S100 -positive folliculo-stellate cells and tumor associated macrophages.

Results

We identified 2 types of cells, with positive immunohistochemical reaction to EGFR in pituitary tumors with negative reaction to EGFR. In some adenomas, we identified, at the periphery of the tumor, an important accumulation of tumor associated macrophages. In these cells, we identified a strong expression of the receptor EGFR. We identified a strong expression of EGFR in folliculostellate cells with a homogenous or granular cytoplasmatic pattern.Both adherent and gap junctions are between folliculostellate cells and between folliculostellate cells and endocrine cells. These cells are also positive for GFAP (glial fibrillary acidic protein), suggesting that this cell type may represent an astrocyte – or microglia – like cell type. Our observations support older findings, notably the increased activity of folliculostellate cells under pathological conditions, their phagocytic activity and their capacity to secrete angiogenic growth factors, suggesting that folliculostellate cells may be involved in basement membrane remodeling, tumoral neoangiogenesis and tumoral expansion.

Discussions and conclusions

The role of folliculostellate cells expressing EGFR in pituitary adenomas has not been studied until now. Clearly, the tumor microenvironment is a major component of pituitary adenomas that holds promise for targeted therapies.We need to better characterize the composition of this microenvironment, influencing the tumor behavior and the response to therapy