Endocrine Abstracts

Background: Pituitary adenomas(PAs) comprise 10%–25% of all intracranial tumors, the majority of them being benign. But 35% of all PAs are considered invasive, having a higher recurrence rate than benign ones.

Objectives: We analyzed the expression of different angiogenic growth factors and their receptors in PAs and identified correlations with the hormone profile that could explain their behavior and prognosis.

Methods: Our study included 92 cases: 10 normal pituitary glands harvested at autopsy and 82 cases of PAs, removed through transsphenoidal approach.We used the hematoxylin eosin stain, immunohistochemistry and the in situ hybridization technique,the RNA scope,which allowed visualization of single mRNA molecules in individual cells, the latter method representing an original aspect of our study.

Results: We obtained a statistically significant correlation between VEGF expression and hormonal profile in somatotroph and lactotroph adenomas;VEGF expression in somatotroph adenomas was associated with an aggressive phenotype. VEGF165b (the inhibitory fraction of VEGF) showed an increased expression predominantly in acidophil PAs; the increased expression of VEGF165b correlated with VEGF overexpression in only 18% of PAs. PDGF-A showed a positive correlation with prolactin secretion; PDGF-B showed a positive correlation with growth hormone secretion. Somatotroph and lactotroph adenomas showed increased expression of EG-VEGF with positive correlation with EGFR overexpression, promoting survival of tumor cells. Acidophil PAs, predominantly lactotroph ones, showed a correlation of EG-VEGF overexpression with Ki67 index.HER2 correlated with prolactin secretion and a potential HER2/HER3 heterodimerization could be a marker of aggressivity of prolactinomas. HER2-correlated with bihormonal PAs, possibly indicating an unfavorable prognosis.EGFR correlated with bihormonal PAs,expressing prolactin.

Conclusions: Our results sustain the recently developed scientific theory which implies the existence of different molecular forms of PAs within the same morphopathological forms; these molecular forms explain the differences in behavior and prognosis of PAs and could pave the way for personalized therapy.