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Published in: Pituitary 6/2022

06-09-2022 | Acromegaly

Characterization of sporadic somatotropinomas with high GIP receptor expression

Authors: Olivia Faria, Renan Lyra Miranda, Carlos Henrique de Azeredo Lima, Alexandro Guterres, Nina Ventura, Monique Alvares Barbosa, Aline Helen da Silva Camacho, Elisa Baranski Lamback, Felipe Andreiuolo, Leila Chimelli, Leandro Kasuki, Mônica R. Gadelha

Published in: Pituitary | Issue 6/2022

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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.
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Metadata
Title
Characterization of sporadic somatotropinomas with high GIP receptor expression
Authors
Olivia Faria
Renan Lyra Miranda
Carlos Henrique de Azeredo Lima
Alexandro Guterres
Nina Ventura
Monique Alvares Barbosa
Aline Helen da Silva Camacho
Elisa Baranski Lamback
Felipe Andreiuolo
Leila Chimelli
Leandro Kasuki
Mônica R. Gadelha
Publication date
06-09-2022
Publisher
Springer US
Published in
Pituitary / Issue 6/2022
Print ISSN: 1386-341X
Electronic ISSN: 1573-7403
DOI
https://doi.org/10.1007/s11102-022-01272-6

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