title: Pituitary tumors and hyperplasia in multiple endocrine neoplasia type 1 syndrome (MEN1): a case-control study in a series of 77 patients versus 2509 non-MEN1 patients.
abstract: Patients affected by the multiple endocrine neoplasia type I syndrome (MEN1) display a high incidence of pituitary adenomas, though it is still unknown whether these pituitary tumors have specific pathologic features that would distinguish them from sporadic pituitary adenomas. Pituitary tissue specimens of 77 MEN1 patients from the GTE (Groupe d'étude des Tumeurs Endocrines) register were compared with unselected 2509 non-MEN1 sporadic pituitary tumors and also to a control subgroup of 296 cases, where 1 MEN1 tumor was matched with 4 sporadic tumors of the same hormonal immunoprofile. Sex, age, size, and invasiveness of tumors, and menin gene mutations were documented. Histologic analysis took into account 33 items, including immunocytochemical data, the proliferative marker Ki-67, and an examination of the juxtatumoral pituitary. MEN1 tumors were significantly larger and more often invasive by histology. MEN1 patients with large pituitary tumors (grade IV) were younger than non-MEN1 patients. MEN1 tumors had no other characteristic histologic features and no predominance of any one hormone producing subtype. However, plurihormonal adenomas versus monohormonal and nonimmunoreactive adenomas were more frequent in MEN1 tumors (39%) than in the control non-MEN1 group (P = 0.001). Especially, the growth hormone and prolactin plurihormonality with unusual association with follicle-stimulating hormone, luteinizing hormone, or adrenocorticotropic hormone was more frequent in MEN1 tumors. In addition, multiple adenomas were significantly more frequent (4% vs. 0.1%; P < 0.0001), especially prolactin-adrenocorticotropic hormone. Somatotroph hyperplasia, with or without a microadenoma was found in only 3 MEN1 patients, with growth hormone-releasing hormone hypersecretion by a pancreatic tumor in 2 of them. All types of mutation were observed, including frameshifts, nonsenses, missenses, and 1 case of germline MEN1 encompassing large deletion, strongly suggesting the absence of any phenotype-genotype correlation.
authors.affiliation: INSERM, U842, Lyon, F-69372, France. jacqueline.trouillas@recherche.univ-lyon1.fr
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Trouillas
authors.forename: Françoise
authors.initials: F
authors.lastname: Labat-Moleur
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sturm
authors.forename: Michèle
authors.initials: M
authors.lastname: Kujas
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Heymann
authors.forename: Dominique
authors.initials: D
authors.lastname: Figarella-Branger
authors.forename: Martine
authors.initials: M
authors.lastname: Patey
authors.forename: Marc
authors.initials: M
authors.lastname: Mazucca
authors.forename: Evelyne
authors.initials: E
authors.lastname: Decullier
authors.forename: Bruno
authors.initials: B
authors.lastname: Vergès
authors.forename: Olivier
authors.initials: O
authors.lastname: Chabre
authors.forename: Alain
authors.initials: A
authors.lastname: Calender
mesh_terms: D000236:Adenoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D005640:Follicle Stimulating Hormone / Q000032:analysis; D015972:Gene Expression Regulation, Neoplastic; D019382:Human Growth Hormone / Q000032:analysis; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D007986:Luteinizing Hormone / Q000032:analysis; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D009154:Mutation; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010902:Pituitary Gland / Q000737:chemistry / Q000473:pathology*; D010911:Pituitary Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D011388:Prolactin / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D013972:Thyrotropin / Q000032:analysis
chemical_list: D019394:Ki-67 Antigen; C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin