Clinicopathological Investigation of Vascular Endothelial Growth Factor and von Hippel-Lindau Gene-Related Protein Expression in Immunohistochemically Negative Pituitary Adenoma - Possible Involvement in Tumor Aggressiveness

Objectives. Immunohistochemically negative pituitary adenoma is known to be relatively indolent, but a few aggressive and highly vascular cases have been reported, which sometimes show high expression of vascular endothelial growth factor (VEGF). Methods. The present study investigated the relationship between high expression of VEGF and the clinical character of pituitary adenomas in 30 cases of immunohistochemically negative pituitary adenomas using immunohistochemical staining with monoclonal VEGF antibody and related upstream factors, including von Hippel-Lindau gene-related protein (pVHL). Correlations between the histological findings and the clinical characteristics were investigated. Results. Immunohistochemical staining using VEGF antibody showed high expression in 7 (23.3%) and low expression in 23 (76.7%) cases, and pVHL staining showed high expression in 24 (80%) and low expression in 6 (20%) cases. The pVHL low expression group showed significantly higher expression of VEGF (p = 0.005019), and significantly higher recurrence or regrowth rate (p = 0.04535) than the pVHL high expression group, whereas Ki-67 labeling index of >3% also showed significant correlation with recurrence or regrowth rate (p = 0.01745). However, there was no significant correlation between pVHL staining and Ki-67 labeling index (p = 0.49978). Conclusion. Low expression of pVHL with high expression of VEGF may be involved in the unusual aggressive clinical course in some pituitary adenomas.