title: Immunohistochemical properties of silent corticotroph adenoma and Cushing's disease.
abstract: Proopiomelanocortin processing in corticotroph cells is known to be operated by prohormone convertase (PC) 1/3 which is activating several pro-proteins and prohormones by intracellular limited proteolysis processing. In this study, we hypothesized that PC1/3 expression differs between Cushing's disease (CD) and silent corticotroph adenoma (SCA), and investigated whether PC1/3 expression is involved in the adrenocorticotropin (ACTH) silence of SCA. We performed immunohistochemical analysis of pituitary adenoma specimens for six adenohypophysial hormones, PC1/3 and chromogranin A (CgA). Subjects for this study consisted of 12 anterior pituitary adenomas of CD (1 male, 11 female; 14-70 years old) and 31 non-functioning adenomas (23 male, 8 female; 32-71 years old).ACTH immunoreactivity was observed in all of CD and three of 31 non-functioning adenomas. The three cases diagnosed as SCA were also positive for growth hormone and follicle-stimulating hormone. Cushing's adenomas and SCAs were all positive for PC1/3. PC1/3-positive cells did not always colocalize with ACTH but some of them colocalized with CgA in SCAs. Even if PC1/3 is not present in corticotroph cells, PC1/3 immunoreactivity in SCA may originate from CgA-positive cells. We conclude that immunohistochemistry for PC1/3 is not helpful for differential diagnosis between CD and SCA in clinical practice, though the regulation of PC1/3 expression is likely to be an important etiological factor in ACTH silence of SCA. The diversity of immunohistochemical properties of SCA leads us to speculate that it is not a single entity and may be a general diagnostic term for adenomas of varying etiology.
authors.affiliation: Department of Medicine, Second Division, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Iino
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oki
authors.forename: Fumie
authors.initials: F
authors.lastname: Matsushita
authors.forename: Miho
authors.initials: M
authors.lastname: Yamashita
authors.forename: Chiga
authors.initials: C
authors.lastname: Hayashi
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Miura
authors.forename: Shigeru
authors.initials: S
authors.lastname: Nishizawa
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000236:Adenoma / Q000378:metabolism*; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D000368:Aged; D053379:Chromogranin A / Q000097:blood; D003346:Corticotropin-Releasing Hormone; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone; D013007:Growth Hormone-Releasing Hormone; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D043484:Proprotein Convertases / Q000097:blood; D013972:Thyrotropin
chemical_list: D053379:Chromogranin A; D019382:Human Growth Hormone; D007987:Gonadotropin-Releasing Hormone; D000324:Adrenocorticotropic Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D003346:Corticotropin-Releasing Hormone; D013007:Growth Hormone-Releasing Hormone; D043484:Proprotein Convertases