*3.3. Expressions of VEGF-Related Molecules and MVD*

Expressions of VEGF-A and VEGFR1 were significantly higher in the CS (+) group than in the CS (−) group (VEGF-A: *p* = 0.033, VEGFR1: *p* = 0.04) (Figure 2). VEGFR2 expression showed no significant difference between the two groups (*p* = 0.28). VEGF-A and VEGFR1 were expressed on not only endothelial cells, but also on tumor cells. MVD showed no significant difference between the two groups (*p* = 0.42; Figure 2), and the average of all cases in both groups, 24.9/3HPF, was equivalent to that of other central nervous tumors with high vasculatures, previously described [19]. Expression of HIF-1α showed no significant difference between the two groups (*p* = 0.88; Figure 2).

**Figure 1.** Analysis of classical histological atypical features for invasive non-functional pituitary neuroendocrine tumors (NF-PitNETs). The existence of CS invasion was evaluated by gadolinium (Gd)-enhanced T1-weighted images. There were no significant differences in Ki-67 and p53 expression or mitotic count between NF-PitNETs with CS invasion and NF-PitNETs without CS invasion (Ki-67 and mitotic count, student's *t*-test; p53, chi-squared test). Black arrow: tumor cell showing positive Ki-67 expression (Original magnification, ×20).

**Figure 2.** Expressions of VEGF-A related molecules in NF-PitNETs. Immunohistochemical analysis of VEGF-A, VEGFR1, VEGFR2, CD34, and HIF-1. Typical examples of each staining are shown in both groups. Black arrow: tumor cells showing positive VEGFR1 expression. V: vascular structure (original magnification, ×20). Statistical analysis of each staining is shown. Expressions of VEGF-A and VEGFR1 are significantly higher in the CS (+) group than in the CS (−) group (VEGF-A: *p* = 0.033, VEGFR1: *p* = 0.040). Expressions of VEGFR2 and HIF-1α do not reach statistical significance (VEGFR2: *p* = 0.28, HIF1-α: *p* = 0.88). MVD shows no significant difference between the two groups (*p* = 0.42). Data represent the mean ± standard error of mean (VEGF-A, VEGFR1, VEGFR2 and HIF-1α, chi-squared test; MVD, student's *t*-test).
