Lloyd et al. examined 148 human pituitary adenomas for VEGF protein expression by immunohistochemistry, and showed positive staining in all groups with stronger staining in GH, ACTH, TSH, and gonadotroph adenomas and in pituitary carcinomas [27]. Our study detected 190 positive VEGF expression cases in 197 PAs and 58.9% of check details them are in high expression level, including 60.7% of PRL-secreting PAs, 78.4% FSH-secreting PAs, 51.9% ACTH-secreting PAs and 57.1% non-functioning

PAs. Niveiro et al. investigated VEGF expression in 60 human pituitary adenomas, and found that low expression of VEGF was seen predominantly in prolactin cell adenomas, and high in non-functioning adenomas, which is different from our data that 60.7% of prolactin cell adenomas verses 57.1% non-functioning adenomas [11]. Moreover, VEGF was considered also involved in conventional medical therapy for PAs. Octreotide was reported to down-regulate VEGF expression to achieve antiangiogenic effects on PAs see more [28]. Gagliano et al. demonstrated that cabergoline reduces cell viability in non-functioning pituitary adenomas by inhibiting VEGF secretion, of which the modulation might mediate the effects of DA agonists on cell proliferation in non-functioning adenoma [29]. Interestingly, in present study, we did GS-9973 spearman’s rank correlation analysis and found that D2R expression did not show a

correlation with VEGF expression. Although it is prospective to treat PAs by anti-VEGF, up to now, only one case of PA has been reported to be cured by bevacizumab [6]. The mechanisms of VEGF in PA genesis and progression are still unclear. More studies are needed to investigate the effects of anti-VEGF therapy on PA patients. To confirm the results, we also detected the expression of D2R, MGMT and VEGF by using western blot. The data supported the results of immunohistochemical staining. Two samples were selected for each PAs subtype. The positive expression of western blot indicated the immunohistochemical staining is available, and the thickness differences of the blot band revealed the expression level differences

in separate sample. Moreover, by spearman’s rank correlation analysis, we found that MGMT expression was positively associated with D2R and VEGF expression in PAs. As far Nintedanib (BIBF 1120) as we know, it is the first time to report the association of D2R and MGMT expression which is positive. Only one report by Moshkin et al. has ever mentioned the association of MGMT and VEGF expression in PA. They demonstrated a progressive regrowth and malignant transformation of a silent subtype 2 pituitary corticotroph adenoma, with significant VEGF and MGMT immunopositivity [30]. The association between VEGF and MGMT expression in PAs need further investigations, as well as D2R and MGMT expression. In addition, we analyzed the association of D2R, MGMT and VEGF expression with clinical features of PAs, but no association was found.