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.
Vidal
S
S
Department of Laboratory Medicine, St. Michael's Hospital, University of Toronto, Ontario, Canada.
Stefaneanu
L
L
Kovacs
K
K
Scheithauer
B W
BW
D000236:Adenoma / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008025:Ligases; D008297:Male; D008875:Middle Aged; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D010907:Pituitary Hormones / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein
D010907:Pituitary Hormones; D011506:Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human