title: The changing faces of corticotroph cell adenomas: the role of prohormone convertase 1/3.
abstract: The spectrum of corticotroph cell adenomas is very wide. Though rarely, silent corticotroph cell adenomas (SCA) may transform into corticotroph cell adenomas associated with Cushing's disease (CD). The aim of the study was to investigate the role of prohormone convertase 1/3 (PC1/3) in the transformation of SCA into CD. We reviewed the records of 1259 consecutive endoscopic endonasal procedures for pituitary adenomas from 1998 to 2013. Of these, 132 were CD and 44 were SCA. During the follow-up, three patients with SCA showed a clear transformation from SCA into CD and underwent surgery once again to remove the recurrent tumour. The PC1/3 expression was analysed by both immunohistochemistry and quantitative real time-polymerase chain reaction (qRT-PCR) in primary and recurrent tumours. The immunohistochemical PC1/3 expression was negative or weak in the three patients in the initial phase of SCA, while a strong expression was observed in the majority of neoplastic cells in tissue specimens obtained from the same three patients at the time of recurrence as CD. The immunohistochemical PC1/3 expression showed a strict correlation with the PC1/3 levels obtained by qRT-PCR. In 14 cases of SCA with no change of phenotype during the follow-up, the immunohistochemical PC1/3 expression was low and strictly associated with the level of PC1/3 obtained by qRT-PCR both in primary (14/14 cases) and in recurrent tumours (4/4 cases). Our study provides insight into the crucial role of the PC1/3 protein in the transformation of phenotype from SCA to CD.
authors.affiliation: Department of Pathology, Rizzoli Institute, Bologna, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Righi
authors.affiliation: IRCCS Institute of Neurological Sciences of Bologna (ISNB), Bellaria Hospital, Via Altura, 3, Bologna, 40139, Italy. marcoff196@gmail.com.
authors.forename: Marco
authors.initials: M
authors.lastname: Faustini-Fustini
authors.affiliation: Department of Biomedical and Neuro-Muscular Sciences, Section of Anatomic Pathology 'M.Malpighi' at Bellaria Hospital, University of Bologna, Bologna, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Morandi
authors.affiliation: Department of Biomedical and Neuro-Muscular Sciences, Section of Anatomic Pathology 'M.Malpighi' at Bellaria Hospital, University of Bologna, Bologna, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Monti
authors.affiliation: Department of Biomedical and Neuro-Muscular Sciences, Section of Anatomic Pathology 'M.Malpighi' at Bellaria Hospital, University of Bologna, Bologna, Italy.
authors.forename: Sofia
authors.initials: S
authors.lastname: Asioli
authors.affiliation: Department of Neurosurgery, Center of Pituitary Tumors and Endoscopic Skull Base Surgery, IRCCS Institute of Neurological Sciences of Bologna (ISNB), Bellaria Hospital, Bologna, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Mazzatenta
authors.affiliation: Department of Neuroradiology, IRCCS Institute of Neurological Sciences of Bologna (ISNB), Bologna, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Bacci
authors.affiliation: Department of Biomedical and Neuro-Muscular Sciences, Section of Anatomic Pathology 'M.Malpighi' at Bellaria Hospital, University of Bologna, Bologna, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Foschini
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000201:enzymology* / Q000473:pathology; D000236:Adenoma / Q000201:enzymology* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D045664:Proprotein Convertase 1 / Q000378:metabolism*
chemical_list: D045664:Proprotein Convertase 1
keywords: Cushing’s disease; Metamorphosis; Pituitary adenoma; Prohormone convertase