SST5 expression and USP8 mutation in functioning and silent corticotroph pituitary tumors

Objective: Somatostatin receptor type 5 (SST5) is inconsistently expressed by corticotroph tumors, with higher expression found in corticotropinomas havin g ubiquitin-specific protease 8 (USP8) mutations. Aims were to study the correlation between characteristics of corticotropinomas and SST5 expres...

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Main Authors: Solène Castellnou, Alexandre Vasiljevic, Véronique Lapras, Véronique Raverot, Eudeline Alix, Françoise Borson-Chazot, Emmanuel Jouanneau, Gérald Raverot, Hélène Lasolle
Format: Article
Language:English
Published: Bioscientifica 2020-03-01
Series:Endocrine Connections
Subjects:
Online Access:https://ec.bioscientifica.com/view/journals/ec/9/3/EC-20-0035.xml
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author Solène Castellnou
Alexandre Vasiljevic
Véronique Lapras
Véronique Raverot
Eudeline Alix
Françoise Borson-Chazot
Emmanuel Jouanneau
Gérald Raverot
Hélène Lasolle
author_facet Solène Castellnou
Alexandre Vasiljevic
Véronique Lapras
Véronique Raverot
Eudeline Alix
Françoise Borson-Chazot
Emmanuel Jouanneau
Gérald Raverot
Hélène Lasolle
author_sort Solène Castellnou
collection DOAJ
description Objective: Somatostatin receptor type 5 (SST5) is inconsistently expressed by corticotroph tumors, with higher expression found in corticotropinomas havin g 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 five 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 three patients (IRS 0, 2 and 6), while a four-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.
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spelling doaj.art-021de8faee9d4d7f94032fa417e26edd2022-12-22T01:43:45ZengBioscientificaEndocrine Connections2049-36142049-36142020-03-0193243253https://doi.org/10.1530/EC-20-0035SST5 expression and USP8 mutation in functioning and silent corticotroph pituitary tumorsSolène Castellnou0Alexandre Vasiljevic1Véronique Lapras2Véronique Raverot3Eudeline Alix4Françoise Borson-Chazot5Emmanuel Jouanneau6Gérald Raverot7Hélène Lasolle8Service d’Endocrinologie, Centre de Référence des Maladies Rares de l’Hypophyse HYPO, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France; Université Lyon 1, Villeurbanne, FranceUniversité Lyon 1, Villeurbanne, France; Centre de Biologie et Pathologie Est, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France; INSERM U1052, CNRS, UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, FranceService de Radiologie, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, FranceLaboratoire d’Hormonologie, Centre de Biologie et Pathologie Est, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, FranceDépartement de Cytogénétique, Centre de Biologie et Pathologie Est, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, FranceService d’Endocrinologie, Centre de Référence des Maladies Rares de l’Hypophyse HYPO, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France; Université Lyon 1, Villeurbanne, France Université Lyon 1, Villeurbanne, France; INSERM U1052, CNRS, UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France; Service de Neurochirurgie, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, FranceService d’Endocrinologie, Centre de Référence des Maladies Rares de l’Hypophyse HYPO, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France; Université Lyon 1, Villeurbanne, France; INSERM U1052, CNRS, UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France Service d’Endocrinologie, Centre de Référence des Maladies Rares de l’Hypophyse HYPO, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France; Université Lyon 1, Villeurbanne, France; INSERM U1052, CNRS, UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, FranceObjective: Somatostatin receptor type 5 (SST5) is inconsistently expressed by corticotroph tumors, with higher expression found in corticotropinomas havin g 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 five 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 three patients (IRS 0, 2 and 6), while a four-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.https://ec.bioscientifica.com/view/journals/ec/9/3/EC-20-0035.xmlsst5corticotroph pituitary tumorsusp8pasireotide
spellingShingle Solène Castellnou
Alexandre Vasiljevic
Véronique Lapras
Véronique Raverot
Eudeline Alix
Françoise Borson-Chazot
Emmanuel Jouanneau
Gérald Raverot
Hélène Lasolle
SST5 expression and USP8 mutation in functioning and silent corticotroph pituitary tumors
Endocrine Connections
sst5
corticotroph pituitary tumors
usp8
pasireotide
title SST5 expression and USP8 mutation in functioning and silent corticotroph pituitary tumors
title_full SST5 expression and USP8 mutation in functioning and silent corticotroph pituitary tumors
title_fullStr SST5 expression and USP8 mutation in functioning and silent corticotroph pituitary tumors
title_full_unstemmed SST5 expression and USP8 mutation in functioning and silent corticotroph pituitary tumors
title_short SST5 expression and USP8 mutation in functioning and silent corticotroph pituitary tumors
title_sort sst5 expression and usp8 mutation in functioning and silent corticotroph pituitary tumors
topic sst5
corticotroph pituitary tumors
usp8
pasireotide
url https://ec.bioscientifica.com/view/journals/ec/9/3/EC-20-0035.xml
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