Characterization of sporadic somatotropinomas with high GIP receptor expression.

Autor: Faria O; 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.; Neuroradiology Department, Samaritano Hospital, São Paulo, Brazil.; Neuroradiology Department, Grupo fleury, São Paulo, Brazil., Miranda RL; Neuropathology and Molecular Genetics Laboratory, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil.; Neuroradiology Department, Samaritano Hospital, São Paulo, Brazil.; Neuroradiology Department, Grupo fleury, São Paulo, Brazil., de Azeredo Lima CH; Neuropathology and Molecular Genetics Laboratory, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil.; Neuroradiology Department, Samaritano Hospital, São Paulo, Brazil.; Neuroradiology Department, Grupo fleury, São Paulo, Brazil., Guterres A; Neuropathology and Molecular Genetics Laboratory, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil.; Neuroradiology Department, Samaritano Hospital, São Paulo, Brazil.; Neuroradiology Department, Grupo fleury, São Paulo, Brazil., Ventura N; Radiology Division, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil.; Radiology Division, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal Do Rio de Janeiro, Rio de Janeiro, Brazil.; Neuroradiology Department, Samaritano Hospital, São Paulo, Brazil.; Neuroradiology Department, Grupo fleury, São Paulo, Brazil., Barbosa MA; Radiology Division, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil.; Neuroradiology Department, Samaritano Hospital, São Paulo, Brazil.; Neuroradiology Department, Grupo fleury, São Paulo, Brazil., da Silva Camacho AH; Neuropathology and Molecular Genetics Laboratory, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil.; Neuroradiology Department, Samaritano Hospital, São Paulo, Brazil.; Neuroradiology Department, Grupo fleury, São Paulo, Brazil., Lamback EB; 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.; Neuropathology and Molecular Genetics Laboratory, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil.; Neuroradiology Department, Samaritano Hospital, São Paulo, Brazil.; Neuroradiology Department, Grupo fleury, São Paulo, Brazil.; Neuroendocrinology Division, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil., Andreiuolo F; Neuropathology and Molecular Genetics Laboratory, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil.; Neuroradiology Department, Samaritano Hospital, São Paulo, Brazil.; Neuroradiology Department, Grupo fleury, São Paulo, Brazil., Chimelli L; Neuropathology and Molecular Genetics Laboratory, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil.; Neuroradiology Department, Samaritano Hospital, São Paulo, Brazil.; Neuroradiology Department, Grupo fleury, São Paulo, Brazil., Kasuki L; 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.; Neuroradiology Department, Samaritano Hospital, São Paulo, Brazil.; Neuroradiology Department, Grupo fleury, São Paulo, Brazil.; Neuroendocrinology Division, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil.; Endocrinology Division, Hospital Federal de Bonsucesso, Rio de Janeiro, Brazil., Gadelha MR; 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.; Neuropathology and Molecular Genetics Laboratory, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil. mgadelha@hucff.ufrj.br.; Neuroradiology Department, Samaritano Hospital, São Paulo, Brazil. mgadelha@hucff.ufrj.br.; Neuroradiology Department, Grupo fleury, São Paulo, Brazil. mgadelha@hucff.ufrj.br.; Neuroendocrinology Division, Instituto Estadual Do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil. mgadelha@hucff.ufrj.br.
Jazyk: angličtina
Zdroj: Pituitary [Pituitary] 2022 Dec; Vol. 25 (6), pp. 903-910. Date of Electronic Publication: 2022 Sep 06.
DOI: 10.1007/s11102-022-01272-6
Abstrakt: 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.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz: