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gsp Mutation Is Not a Molecular Biomarker of Long-Term Response to First-Generation Somatostatin Receptor Ligands in Acromegaly

Wildemberg, Luiz Eduardo ; Henriques, Daniel ; Elias, Paula C. L. ; Lima, Carlos Henrique de A. ; Musolino, Nina R. de Castro ; Camacho, Aline Helen Silva ; Faria, Olivia ; Nazato, Debora ; Abucham, Julio ; Vilar, Lucio ; Mota, Jose Italo ; Huayllas, Martha Katherine P. ; Chimelli, Leila ; Castro, Margaret de ; Kasuki, Leandro ; Gadelha, Mônica R.

Cancers, 2021-09, Vol.13 (19), p.4857 [Periódico revisado por pares]

Basel: MDPI AG

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Título:
gsp Mutation Is Not a Molecular Biomarker of Long-Term Response to First-Generation Somatostatin Receptor Ligands in Acromegaly
Autor: Wildemberg, Luiz Eduardo ; Henriques, Daniel ; Elias, Paula C. L. ; Lima, Carlos Henrique de A. ; Musolino, Nina R. de Castro ; Camacho, Aline Helen Silva ; Faria, Olivia ; Nazato, Debora ; Abucham, Julio ; Vilar, Lucio ; Mota, Jose Italo ; Huayllas, Martha Katherine P. ; Chimelli, Leila ; Castro, Margaret de ; Kasuki, Leandro ; Gadelha, Mônica R.
Assuntos: Acromegaly ; Biomarkers ; Cytokeratin ; Disease control ; Gene expression ; Growth hormone ; Growth hormones ; gsp mutation ; Immunohistochemistry ; Insulin-like growth factor I ; Insulin-like growth factors ; Laboratories ; Ligands ; Medical treatment ; mRNA ; Mutation ; Patients ; Phenotypes ; Polymerase chain reaction ; Protein expression ; Proteins ; Radiation therapy ; Sinuses ; Somatostatin ; somatostatin receptor ligands ; somatotropinoma ; Surgery ; Tumors
É parte de: Cancers, 2021-09, Vol.13 (19), p.4857
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Descrição: Background: It is still controversial if activating mutations in the stimulatory G-protein α subunit (gsp mutation) are a biomarker of response to first generation somatostatin receptor ligands (fg-SRL) treatment in acromegaly. Thus, we aimed to evaluate whether gsp mutation predicts long-term response to fg-SRL treatment and to characterize the phenotype of patients harboring gsp mutations. Methods: GNAS1 sequencing was performed by Sanger. SST2 and SST5 were analyzed by immunohistochemistry (IHC) and real-time RT-PCR. The cytokeratin granulation pattern was evaluated by IHC. Biochemical control was defined as GH < 1.0 ng/mL and normal age-adjusted IGF-I levels. Results: gsp mutation was found in 54 out of 136 patients evaluated. Biochemical control with fg-SRL treatment was similar in gsp+ and gsp- patients (37% vs. 25%, p = 0.219). Tumors harboring gsp mutation were smaller (p = 0.035) and had a lower chance of invading cavernous sinuses (p = 0.001). SST5 protein (p = 0.047) and mRNA (p = 0.013) expression levels were higher in wild-type tumors. Conclusions: In this largest series available in the literature, we concluded that gsp is not a molecular biomarker of response to fg-SRL treatment in acromegaly. However, the importance of its negative association with cavernous sinus invasion and SST5 expression needs to be further investigated.
Editor: Basel: MDPI AG
Idioma: Inglês

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gsp Mutation Is Not a Molecular Biomarker of Long-Term Response to First-Generation Somatostatin Receptor Ligands in Acromegaly

Basel: MDPI AG

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