Digital quantification of somatostatin receptor subtypes 2 and 5 in GH-secreting pituitary tumors.

Immunohistochemistry of somatostatin receptor subtype 2 (SSTR2) can predict response to first-generation somatostatin receptor ligands (fg-SRLs) in acromegaly. Recently, we validated an open-source digital image analysis (DIA) to quantify SSTR2 expression. We aimed to validate the DIA also on SSTR5 in a new cohort of GH-secreting pituitary tumors, with immunohistochemistry performed in a different laboratory, and to correlate fg-SRL response with SSTs expression. SSTR2 and SSTR5 were assessed in 42 GH-secreting pituitary tumors, using a semi-quantitative immunoreactivity score (IRS) and the DIA by use of the open-access software CellProfiler. The DIA calculates the staining intensity and the percentage of positive cells (%PC). We found a good correlation between IRS and DIA for both SSTR2 and SSTR5 (p<0.001), demonstrating the reliability of the DIA in this setting. Response to fg-SRL treatment correlated with SSTR2, but not SSTR5, expression. SSTR2 expression predicted response to fg-SRL. In particular, the identified cut-offs were: IRS ≥ 5 (AUC 0.763; sensitivity 77%, specificity 83%); intensity/area ≥0.106 (AUC 0.833; sensitivity 92%, specificity 83%) and %PC-DIA ≥63.7% (AUC 0.917; sensitivity 92%, specificity 83%). The SSTR2 %PC correlated with treatment response only when evaluated using the DIA, showing a better performance of this method.