{Reference Type}: Journal Article
{Title}: gsp Mutation Is Not a Molecular Biomarker of Long-Term Response to First-Generation Somatostatin Receptor Ligands in Acromegaly.
{Author}: Wildemberg LE;Henriques D;Elias PCL;Lima CHA;Musolino NRC;Camacho AHS;Faria O;Nazato D;Abucham J;Vilar L;Mota JI;Huayllas MKP;Chimelli L;Castro M;Kasuki L;Gadelha MR;
{Journal}: Cancers (Basel)
{Volume}: 13
{Issue}: 19
{Year}: Sep 2021 28
{Factor}: 6.575
{DOI}: 10.3390/cancers13194857
{Abstract}: <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.