title: 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.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  Low expression of pVHL with high expression of VEGF may be involved in the unusual aggressive clinical course in some pituitary adenomas.
authors: Department of Neurosurgery, Tohoku University Graduate School of Medicine , Sendai , Japan.
authors: Yoshiteru
authors: Y
authors: Shimoda
authors: Yoshikazu
authors: Y
authors: Ogawa
authors: Mika
authors: M
authors: Watanabe
authors: Teiji
authors: T
authors: Tominaga
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000737:chemistry; D010911:Pituitary Neoplasms / Q000737:chemistry* / Q000473:pathology; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000032:analysis*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human