Expression of von Hippel-Lindau protein (VHL-P) in nontumorous and adenomatous human pituitaries

We studied the presence of von Hippel-Lindau protein (VHL-P) in 7 nontumorous pituitaries and 68 pituitary adenomas by immunocytochemistry using a polyclonal antibody which detects both normal and mutated forms. In nontumorous pituitary VHL-P was variable expressed in the cytoplasm of most adenohypophysial cells. In addition, weak diffuse staining was noted in the posterior lobe. Among the 53 VHL-P immunopositive adenomas (78%), 32 showed only cytoplasmic, 7 only nuclear, and 14 both cytoplasmic and nuclear immunoreactivity. In densely (8 cases) and sparsely (7 cases) granulated somatotroph adenomas nuclear and weak cytoplasmic immunoreactivity were common; all 4 sparsely granulated lactotroph adenomas had only moderate cytoplasmic immunostaining; all 7 functioning corticotroph adenomas presented intense cytoplasmic immunoreactivity and 4/7 showing nuclear immunostaining as well; all 3 silent subtype 1 adenomas were negative; 7 3/4 silent subtype 2 and 4/7 silent subtype 3 adenomas exhibited only cytoplasmic immunoreactivity; thyrotroph adenomas showed variable patterns from negative in 1/7, to only cytoplasmic in 2/7, nuclear alone in 2/7, or both in 2/7. Only weak, focal cytoplasmic immunoreactivity was noted in gonadotroph adenomas of female (2/4) and male (1/5) type. Lastly, all 4 null cell and 8 oncocytic adenomas showed moderate to intense cytoplasmic immunoreactivity. It can be concluded that the majority of pituitary adenomas express the VHL-P with variable distributions and intensity in different tumor types. The frequent localization of VHL-P in the nuclei of somatotroph adenomas, the least vascularized tumor type, suggests a possible inhibitory role of VHL-P in pituitary angiogenesis.