title: Corticotroph carcinoma presenting as a silent corticotroph adenoma.
abstract: Malignant pituitary tumours are rare and their pathogenesis is not fully understood. We have performed genetic analyses on tissues arising from a pituitary carcinoma that initially presented as a silent corticotroph adenoma but which failed to respond to repeated, aggressive surgical and medical therapy. Loss of heterozygosity (LOH) of known or putative tumour suppressor genes (TSG) was assessed by microsatellite analysis of microdissected tumour and matched patient blood DNA. Clonality of the pituitary tumour samples was analysed by two PCR-based techniques; one employing the highly polymorphic short tandem repeat (STR) within the human androgen receptor allele (HUMARA), another based on a restriction fragment length polymorphism of the X chromosome phosphoglycerokinase (PGK-1) gene. Screening with 9 microsatellite markers demonstrated allelic loss at 3 sites (D1S190, D3S1283 and D10S297) in all tumour samples except the presenting pituitary tumour. X chromosome inactivation analysis demonstrated polyclonality in the original presenting tumour and a metastatic deposit but monoclonality in tissue samples from a second and third transsphenoidal resection. In these cases of tumour recurrence both LOH and X chromosome inactivation suggest that monoclonality arose from preferential clonal growth from the original polyclonal tumour. Polyclonality of the metastatic deposit suggests that this was derived from the presenting tumour, although the LOH pattern indicates that a single clone dominates. The data are consistent with increasing allelic loss associated with tumour dedifferentiation and malignant transformation.
authors.affiliation: School of Postgraduate Medicine, North Staffs Hospital, Stoke on Trent, UK.
authors.forename: William E
authors.initials: WE
authors.lastname: Farrell
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Coll
authors.forename: Richard N
authors.initials: RN
authors.lastname: Clayton
authors.forename: Philip E
authors.initials: PE
authors.lastname: Harris
mesh_terms: D000236:Adenoma / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D003480:Cushing Syndrome / Q000209:etiology; D003937:Diagnosis, Differential; D004303:Dosage Compensation, Genetic; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008279:Magnetic Resonance Imaging; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D010911:Pituitary Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology*
chemical_list: D000324:Adrenocorticotropic Hormone