Solène Castellnou1, Alexandre Vasiljevic2, Veronique Lapras3, Véronique Raverot4, Eudeline Alix5, Françoise Borson-Chazot6, Emmanuel Jouanneau7, Gerald Raverot8, Hélène Lasolle9. 1. S Castellnou, Service d'endocrinologie, Centre de Référence des Maladies Rares de l'Hypophyse HYPO, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France. 2. A Vasiljevic, Centre de Biologie et Pathologie Est, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France. 3. V Lapras, Service de Radiologie, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France. 4. V Raverot, Laboratoire d'hormonologie, Centre de Biologie et Pathologie Est, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France. 5. E Alix, Département de cytogénétique, Centre de Biologie et Pathologie Est, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France. 6. F Borson-Chazot, Service d'Endocrinologie, Centre de Référence des Maladies Rares de l'Hypophyse HYPO, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France. 7. E Jouanneau, Service de Neurochirurgie, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France. 8. G Raverot, Service d'Endocrinologie, Centre de Référence des Maladies Rares de l'Hypophyse HYPO, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France. 9. H Lasolle, Service d'Endocrinologie, Centre de Référence des Maladies Rares de l'Hypophyse HYPO, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France.
Abstract
OBJECTIVE: Somatostatin receptor type 5 (SST5) is inconsistently expressed by corticotroph tumors, with higher expression found in corticotropinomas having ubiquitin-specific protease 8 (USP8) mutations. Aims were to study the correlation between characteristics of corticotropinomas and SST5 expression/USP8 mutation status and to describe the response to pasireotide in 5 patients. DESIGN: Retrospective cohort study. METHODS: Clinico-biochemical, radiological and pathological data of 62 patients, operated for a functioning or silent corticotropinoma between 2013 and 2017, were collected. SST5 expression was measured by immunohistochemistry (clone UMB-4, Abcam, IRS>1 being considered positive) and Sanger sequencing was performed on 50 tumors to screen for USP8 mutations. RESULTS: SST5 expression was positive in 26/62 pituitary tumors. A moderate or strong IRS was found in 15/58 corticotropinomas and in 13/35 functioning corticotropinomas. Among functioning tumors, those expressing SST5 were more frequent in women (22/24 vs 9/15, P=0.04) and had a lower grade (P=0.04) compared to others. USP8 mutations were identified in 13/50 pituitary tumors and were more frequent in functioning compared to silent tumors (11/30 vs 2/20, P=0.05). SST5 expression was more frequent in USP8mut vs USP8wt tumors (10/11 vs 7/19, P=0.007). Among treated patients, normal urinary free cortisol levels were obtained in 3 patients (IRS 0, 2, 6) while a 4-fold decrease was observed in one patient (IRS 4). CONCLUSION: SST5 expression appears to be associated with functioning, USP8mut and lower grade corticotropinomas. A correlation between SST5 expression or USP8mut and response to pasireotide remains to be confirmed.
OBJECTIVE:Somatostatin receptor type 5 (SST5) is inconsistently expressed by corticotroph tumors, with higher expression found in corticotropinomas having ubiquitin-specific protease 8 (USP8) mutations. Aims were to study the correlation between characteristics of corticotropinomas and SST5 expression/USP8 mutation status and to describe the response to pasireotide in 5 patients. DESIGN: Retrospective cohort study. METHODS: Clinico-biochemical, radiological and pathological data of 62 patients, operated for a functioning or silent corticotropinoma between 2013 and 2017, were collected. SST5 expression was measured by immunohistochemistry (clone UMB-4, Abcam, IRS>1 being considered positive) and Sanger sequencing was performed on 50 tumors to screen for USP8 mutations. RESULTS:SST5 expression was positive in 26/62 pituitary tumors. A moderate or strong IRS was found in 15/58 corticotropinomas and in 13/35 functioning corticotropinomas. Among functioning tumors, those expressing SST5 were more frequent in women (22/24 vs 9/15, P=0.04) and had a lower grade (P=0.04) compared to others. USP8 mutations were identified in 13/50 pituitary tumors and were more frequent in functioning compared to silent tumors (11/30 vs 2/20, P=0.05). SST5 expression was more frequent in USP8mut vs USP8wt tumors (10/11 vs 7/19, P=0.007). Among treated patients, normal urinary free cortisol levels were obtained in 3 patients (IRS 0, 2, 6) while a 4-fold decrease was observed in one patient (IRS 4). CONCLUSION:SST5 expression appears to be associated with functioning, USP8mut and lower grade corticotropinomas. A correlation between SST5 expression or USP8mut and response to pasireotide remains to be confirmed.
Authors: Maria Fleseriu; Richard Auchus; Irina Bancos; Anat Ben-Shlomo; Jerome Bertherat; Nienke R Biermasz; Cesar L Boguszewski; Marcello D Bronstein; Michael Buchfelder; John D Carmichael; Felipe F Casanueva; Frederic Castinetti; Philippe Chanson; James Findling; Mônica Gadelha; Eliza B Geer; Andrea Giustina; Ashley Grossman; Mark Gurnell; Ken Ho; Adriana G Ioachimescu; Ursula B Kaiser; Niki Karavitaki; Laurence Katznelson; Daniel F Kelly; André Lacroix; Ann McCormack; Shlomo Melmed; Mark Molitch; Pietro Mortini; John Newell-Price; Lynnette Nieman; Alberto M Pereira; Stephan Petersenn; Rosario Pivonello; Hershel Raff; Martin Reincke; Roberto Salvatori; Carla Scaroni; Ilan Shimon; Constantine A Stratakis; Brooke Swearingen; Antoine Tabarin; Yutaka Takahashi; Marily Theodoropoulou; Stylianos Tsagarakis; Elena Valassi; Elena V Varlamov; Greisa Vila; John Wass; Susan M Webb; Maria C Zatelli; Beverly M K Biller Journal: Lancet Diabetes Endocrinol Date: 2021-10-20 Impact factor: 32.069
Authors: Mateusz Bujko; Paulina Kober; Joanna Boresowicz; Natalia Rusetska; Natalia Zeber-Lubecka; Agnieszka Paziewska; Monika Pekul; Grzegorz Zielinski; Andrzej Styk; Jacek Kunicki; Jerzy Ostrowski; Janusz A Siedlecki; Maria Maksymowicz Journal: J Clin Med Date: 2021-01-20 Impact factor: 4.241