ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2017) 49 EP935 | DOI: 10.1530/endoabs.49.EP935

HER2, EGFR and PDGF family members as potential prognostic markers and their therapeutic implications

Ana Silvia Corlan1, Anca Cimpean1, Marius Raica1, Eugen Melnic2 & Raluca Amalia Ceausu1

1Department of Microscopic Morphology/Histology, Angiogenesis Research Center, University of Medicine and Pharmacy Timisoara, Timisoara, Russia; 2Department of Pathology, Nicolae Testemitanu University of Medicine and Pharmacy, Chisinau, Moldova, Chisinau, Republic of Moldova.

Background: The role of EGFR, HER2, PDGF-A and the axis PDGF-B/ PDGFR-β in the pathogenesis of pituitary adenomas and their correlation with the tumoral immunoprofile are poorly understood.

Materials and methods: The study included 92 cases. We used morphological stains, immunohistochemistry and molecular methods to characterize the tumors.

Results: 33.33% of adenomas showed a positive immunohistochemical reaction for HER2- with a membranous and cytoplasmatic pattern- the first one prevailing. The restriction of HER-2 expression to the membrane was noticed in the basophilic cells of basophilic or mixed adenomas. For the acidophilic cells: the expression of HER2 was mostly cytoplasmatic with a granular pattern. In pure adenomas, the only significant correlation with the expression of HER-2 was shown for prolactinomas. For bihormonal adenomas we obtained a significant correlation of HER-2 with the coexpression of GH-PRL, PRL-LH, TSH-FSH, TSH-LH. The gene amplification pattern confirmed the expression of HER-2 in 33,3% of adenomas positive for HER-2. For adenomas positive for EGFR, we obtained a significant correlation with the coexpression of GH-PRL, PRL-TSH (partial correlation), PRL-ACTH (total correlation). We analyzed the effects of PDGF-A and PDGF-B on adenoma cells, depending on their immunoprofile. For each of these 2 factors, 60–80% of tumor cells were immunohistochemically positive. We obtained data contradictory to the published one: a positive correlation between PDGF-A and prolactin expression. We confirmed the known association between PDGF-B and somatotropinomas.

Discussions and conclusions: We identified a positive correlation between PDGF-B and PDGFR-β expression, implying a role for this axis in the pathogenesis of pituitary adenomas. The FSH-LH association induces the overexpression of HER-2 in pituitary adenomas, specifying a unique subtype of adenomas. We noticed the expression of EGFR in peritumoral macrophages and folliculo-stellate cells, leaving new opportunities for studying the role of folliculo-stelate cells and the pathogenic role of EGFR in these tumors.

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