gsp Mutation Is Not a Molecular Biomarker of Long-Term Response to First-Generation Somatostatin Receptor Ligands in Acromegaly
Luiz Eduardo Wildemberg, Daniel G. Henriques, Paula Condé Lamparelli Elias, Carlos Henrique de Azeredo Lima, Nina Rosa de Castro Musolino, Aline Helen Silva Camacho, Olivia Faria, Debora Nazato, Júlio Abucham, Lúcio Vilar, José Ítalo Soares Mota, Martha Katherine Paniagua Huayllas, Leila Chimelli, Margaret de Castro, Leandro Kasuki, Mônica R. Gadelha
Abstract
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.