Olivia Faria1,2,3, Renan Lyra Miranda4,2,3, Carlos Henrique de Azeredo Lima4,2,3, Alexandro Guterres4,2,3, Nina Ventura5,6,2,3, Monique Alvares Barbosa5,2,3, Aline Helen da Silva Camacho4,2,3, Elisa Baranski Lamback1,4,2,3,7, Felipe Andreiuolo4,2,3, Leila Chimelli4,2,3, Leandro Kasuki1,2,3,7,8, Mônica R Gadelha9,10,11,12,13. 1. Neuroendocrinology Research Center/Endocrinology Division, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal Do Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco, 255, 9° andar, Setor 9F, Rio de Janeiro, 21941-913, Brazil. 2. Neuroradiology Department, Samaritano Hospital, São Paulo, Brazil. 3. Neuroradiology Department, Grupo fleury, São Paulo, Brazil. 4. Neuropathology and Molecular Genetics Laboratory, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil. 5. Radiology Division, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil. 6. Radiology Division, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brazil. 7. Neuroendocrinology Division, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil. 8. Endocrinology Division, Hospital Federal de Bonsucesso, Rio de Janeiro, Brazil. 9. Neuroendocrinology Research Center/Endocrinology Division, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal Do Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco, 255, 9° andar, Setor 9F, Rio de Janeiro, 21941-913, Brazil. mgadelha@hucff.ufrj.br. 10. Neuropathology and Molecular Genetics Laboratory, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil. mgadelha@hucff.ufrj.br. 11. Neuroradiology Department, Samaritano Hospital, São Paulo, Brazil. mgadelha@hucff.ufrj.br. 12. Neuroradiology Department, Grupo fleury, São Paulo, Brazil. mgadelha@hucff.ufrj.br. 13. Neuroendocrinology Division, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil. mgadelha@hucff.ufrj.br.
Abstract
PURPOSE: To analyze the expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in somatotropinomas specimens and compare clinical, biochemical, radiological, therapeutic, molecular, and pathological data among those who overexpressed (GIPR +) and those who did not overexpress (GIPR - ) GIPR. METHODS: Clinical, biochemical, radiological, molecular, and pathological data were collected. GNAS1 sequencing was performed with the Sanger method. Protein expression of somatostatin receptor subtypes 2 and 5 and CAM 5.2 were analyzed by immunohistochemistry. Quantitative real-time PCR was performed to analyze the mRNA expression of GIPR with the TaqMan® method. Positive expression was considered when the fold change (FC) was above 17.2 (GIPR +). RESULTS: A total of 74 patients (54% female) were included. Eighteen tumors (24%) were GIPR + . Gsp mutation was detected in 30 tumors (40%). GIPR + tumors were more frequently densely granulated adenomas (83% vs 47%, p = 0.028). There was no difference in clinical, biochemical, radiological, therapeutic (surgical cure or response to medical therapy), or other pathological features between GIPR + and GIPR - tumors. Twenty-eight out of 56 (50%) GIPR - tumors harbored a gsp mutation, whereas two out of 18 (11%) GIPR + tumors harbored a gsp mutation (p = 0.005). CONCLUSION: We described, for the first time, that GIPR + and gsp mutations are not mutually exclusive, but gsp mutations are less common in GIPR + tumors. GIPR + and GIPR - tumors have similar clinical, biochemical, radiological, therapeutic, and pathological features, with the exception of a high frequency of densely granulated adenomas among GIPR + tumors.
PURPOSE: To analyze the expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in somatotropinomas specimens and compare clinical, biochemical, radiological, therapeutic, molecular, and pathological data among those who overexpressed (GIPR +) and those who did not overexpress (GIPR - ) GIPR. METHODS: Clinical, biochemical, radiological, molecular, and pathological data were collected. GNAS1 sequencing was performed with the Sanger method. Protein expression of somatostatin receptor subtypes 2 and 5 and CAM 5.2 were analyzed by immunohistochemistry. Quantitative real-time PCR was performed to analyze the mRNA expression of GIPR with the TaqMan® method. Positive expression was considered when the fold change (FC) was above 17.2 (GIPR +). RESULTS: A total of 74 patients (54% female) were included. Eighteen tumors (24%) were GIPR + . Gsp mutation was detected in 30 tumors (40%). GIPR + tumors were more frequently densely granulated adenomas (83% vs 47%, p = 0.028). There was no difference in clinical, biochemical, radiological, therapeutic (surgical cure or response to medical therapy), or other pathological features between GIPR + and GIPR - tumors. Twenty-eight out of 56 (50%) GIPR - tumors harbored a gsp mutation, whereas two out of 18 (11%) GIPR + tumors harbored a gsp mutation (p = 0.005). CONCLUSION: We described, for the first time, that GIPR + and gsp mutations are not mutually exclusive, but gsp mutations are less common in GIPR + tumors. GIPR + and GIPR - tumors have similar clinical, biochemical, radiological, therapeutic, and pathological features, with the exception of a high frequency of densely granulated adenomas among GIPR + tumors.
Authors: Cristina L Ronchi; Erika Peverelli; Sabine Herterich; Isabel Weigand; Giovanna Mantovani; Thomas Schwarzmayr; Silviu Sbiera; Bruno Allolio; Jürgen Honegger; Silke Appenzeller; Andrea G Lania; Martin Reincke; Davide Calebiro; Anna Spada; Michael Buchfelder; Joerg Flitsch; Tim M Strom; Martin Fassnacht Journal: Eur J Endocrinol Date: 2015-12-23 Impact factor: 6.664
Authors: Wenya Linda Bi; Peleg Horowitz; Noah F Greenwald; Malak Abedalthagafi; Pankaj K Agarwalla; Wiliam J Gibson; Yu Mei; Steven E Schumacher; Uri Ben-David; Aaron Chevalier; Scott Carter; Grace Tiao; Priscilla K Brastianos; Azra H Ligon; Matthew Ducar; Laura MacConaill; Edward R Laws; Sandro Santagata; Rameen Beroukhim; Ian F Dunn Journal: Clin Cancer Res Date: 2016-10-05 Impact factor: 12.531
Authors: Z A Efstathiadou; A Bargiota; A Chrisoulidou; G Kanakis; L Papanastasiou; A Theodoropoulou; S K Tigas; D A Vassiliadi; M Alevizaki; S Tsagarakis Journal: Pituitary Date: 2015-12 Impact factor: 4.107
Authors: Laurence Katznelson; Edward R Laws; Shlomo Melmed; Mark E Molitch; Mohammad Hassan Murad; Andrea Utz; John A H Wass Journal: J Clin Endocrinol Metab Date: 2014-10-30 Impact factor: 5.958
Authors: S Melmed; F F Casanueva; A Klibanski; M D Bronstein; P Chanson; S W Lamberts; C J Strasburger; J A H Wass; A Giustina Journal: Pituitary Date: 2013-09 Impact factor: 4.107