title: Determination of the proliferation and apoptotic index in adrenocorticotropin-secreting pituitary tumors : comparison between micro- and macroadenomas.
abstract: We investigated the growth fraction and cell loss fraction in a large group of patients with Cushing's disease subdivided according to tumor size. Fifty-one patients, 8 males and 43 females, aged 12 through 61 years (mean age 34.6 +/- 1.5 years), were studied. Thirty-six patients had a microadenoma and the remaining 15 a macroadenoma. Immunohistochemical analysis was performed on paraffin-embedded material using a monoclonal antibody (MIB-1) directed against a proliferation-associated nuclear antigen, Ki-67, to measure the growth fraction. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method, using a monoclonal antibody recognizing areas of DNA fragmentation. Ki-67 labeling index and apoptosis were counted on separate slides in at least 1000 evaluable cells. Patients with a macroadenoma had a significantly higher value of Ki-67 index (9.3 +/- 2.7%) than patients with microadenoma (2.8 +/- 0.5%; P < 0.002), whereas the apoptotic index was not significantly different in the two groups (1.7 +/- 0.8% in macroadenomas versus 0.8 +/- 0.3% in microadenomas). Our study shows that ACTH-secreting macroadenomas are characterized by a higher cell growth fraction than microadenomas, whereas the cell loss fraction is not different. A high proliferation rate seems to play a major role in determining the progression from small to large pituitary tumors in Cushing's disease.
authors.affiliation: Pituitary Unit of the Department of Neurosurgery, IRCCS San Raffaele, University of Milano, Milano, Italy. losa.marco@hsr.it
authors.forename: M
authors.initials: M
authors.lastname: Losa
authors.forename: R L
authors.initials: RL
authors.lastname: Barzaghi
authors.forename: P
authors.initials: P
authors.lastname: Mortini
authors.forename: A
authors.initials: A
authors.lastname: Franzin
authors.forename: F
authors.initials: F
authors.lastname: Mangili
authors.forename: M R
authors.initials: MR
authors.lastname: Terreni
authors.forename: M
authors.initials: M
authors.lastname: Giovanelli
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D000911:Antibodies, Monoclonal; D017209:Apoptosis; D002455:Cell Division; D002648:Child; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology
chemical_list: D000911:Antibodies, Monoclonal; D019394:Ki-67 Antigen; D000324:Adrenocorticotropic Hormone