title: Giant pituitary adenomas: pathologic-radiographic correlations and lack of role for p53 and MIB-1 labeling.
abstract: Giant pituitary adenomas, with diameter ≥4 cm, were formerly considered rare and not surgically approachable. Few United States-based series exist. We reviewed our 10-year experience with these tumors and identified 17 patients, 11 male and 6 female, aged 27 to 65 years. Twelve of 17 cases were either gonadotroph or null cell adenomas and 5 were giant prolactinomas. By neuroimaging, all invaded the cavernous sinus(es) and tumors in 13 patients invaded the skull base. Despite massive size, only 5 showed apoplectic clinical and neuroimaging features. When present, this feature occasionally prompted preoperative consideration of craniopharyngioma. Transsphenoidal surgical excision was possible in all patients, with 3 undergoing planned second-stage reoperations and 2 requiring a second surgery for recurrence (both at 6-year intervals). Despite the aggressive features of massive size and cavernous sinus invasion, mitotic rates and immunohistochemistry (IHC) labeling for p53 and MIB-1, features alleged to be associated with atypical adenomas, were minimally increased. Absence of a role for TP53 and cell cycle markers was further verified on a subset of our cases by microarray and quantitative reverse transcription polymerase chain reaction analyses. Five giant gonadotroph adenomas were compared with 7 nonaggressive, nongiant gonadotroph cell adenomas, and no statistically significant changes in transcript levels of MIB-1 (MKI67) or TP53 were observed. A number of other genes, however, did show differential gene expression. In conclusion, most giant pituitary adenomas are gonadotroph cell adenomas or giant prolactinomas in men. Microarray profiling validates the IHC impression that MIB-1 and p53 IHC do not correlate with aggressive features in the most common type of giant adenoma.
authors.affiliation: Department of Pathology, The University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Madsen
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Borges
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Knox
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Michaelis
authors.forename: Mei
authors.initials: M
authors.lastname: Xu
authors.forename: Kevin O
authors.initials: KO
authors.lastname: Lillehei
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Wierman
authors.forename: Bette Kay
authors.initials: BK
authors.lastname: Kleinschmidt-DeMasters
mesh_terms: D000236:Adenoma / Q000737:chemistry / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D002426:Cavernous Sinus / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D052681:Gonadotrophs / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis* / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D020411:Oligonucleotide Array Sequence Analysis; D010911:Pituitary Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D015175:Prolactinoma / Q000737:chemistry / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D012333:RNA, Messenger / Q000032:analysis; D011859:Radiography; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019291:Skull Base / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics
chemical_list: D019394:Ki-67 Antigen; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53