title: Markers of cell proliferation in a GH-producing adenoma of a patient treated with pegvisomant.
abstract: We report our findings on markers of cell proliferation (Ki-67 labelling index and topoisomerase-alpha expression) in a somatotroph pituitary tumour before and after exposure to pegvisomant, a GH receptor antagonist developed for the treatment of acromegaly. Specimens from two separate pituitary operations, separated by a period of 17 years that included 4 years of pegvisomant treatment, were stained for markers of cellular proliferation. Ki-67 labelling index and topoisomerase-alpha expression were both markedly greater (1-3% compared with 0-0.5% and 15-80% compared with 2-10% respectively) in the pegvisomant-exposed tumour compared with the earlier specimen. Clearly, caution must be exercised when interpreting findings from a single case, particularly one sufficiently refractory to conventional therapies to require treatment with pegvisomant. However, our data reinforce the requirement for careful radiological surveillance of the pituitary in the context of a drug that does not target the tumour responsible and where serum GH cannot serve as a marker of disease activity or tumour size.
authors.affiliation: Department of Endocrinology, St Bartholomew's Hospital, West Smithfield, London, UK. w.m.drake@qmul.ac.uk
authors.forename: W M
authors.initials: WM
authors.lastname: Drake
authors.forename: D M
authors.initials: DM
authors.lastname: Berney
authors.forename: K
authors.initials: K
authors.lastname: Kovacs
authors.forename: J P
authors.initials: JP
authors.lastname: Monson
mesh_terms: D000172:Acromegaly / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000236:Adenoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D000293:Adolescent; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D002455:Cell Division; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D019382:Human Growth Hormone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D004250:DNA Topoisomerases, Type II; C406545:pegvisomant