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

Background: It is still controversial if activating mutations in the stimulatory G-protein α subunit ( mutation) are a biomarker of response to first generation somatostatin receptor ligands (fg-SRL) treatment in acromegaly. Thus, we aimed to evaluate whether mutation predicts long-term response to fg-SRL treatment and to characterize the phenotype of patients harboring mutations.

Methods: 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: mutation was found in 54 out of 136 patients evaluated. Biochemical control with fg-SRL treatment was similar in + and - patients (37% vs. 25%, = 0.219). Tumors harboring mutation were smaller ( = 0.035) and had a lower chance of invading cavernous sinuses ( = 0.001). SST5 protein ( = 0.047) and mRNA ( = 0.013) expression levels were higher in wild-type tumors.

Conclusions: In this largest series available in the literature, we concluded that 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.