Digital quantification of somatostatin receptor subtype 2a immunostaining: a validation study

Area of Science:

• Endocrinology
• Oncology
• Pathology

Background:

• Somatostatin receptor subtype 2a (SST2) is a key target in neuroendocrine tumors.
• Accurate quantification of SST2 expression is crucial for treatment selection and monitoring.
• Existing semi-quantitative methods can be subjective and lack reproducibility.

Purpose of the Study:

• To develop and validate an open-source, reproducible digital quantitative analysis (DIA) for SST2 immunostaining.
• To assess SST2 expression in pancreatic neuroendocrine tumors (panNETs) and growth hormone (GH)-secreting pituitary adenomas (GHomas).
• To compare the novel DIA protocol with the established semi-quantitative immunoreactivity score (IRS).

Main Methods:

• A novel DIA protocol was developed for SST2 immunostaining in formalin-fixed paraffin-embedded tissues.
• Analysis included staining intensity/area and percentage of positive cells (%PC).
• Inter-observer agreement was assessed using concordance correlation coefficient (CCC).

Main Results:

• The DIA demonstrated excellent inter-observer agreement in both panNETs (CCC 0.935-0.983) and GHomas (CCC 0.963-0.997).
• DIA results strongly correlated with the semi-quantitative IRS for both intensity/area and %PC.
• In GHomas, SST2 expression quantified by DIA correlated with biochemical response to somatostatin receptor ligands.

Conclusions:

• The developed DIA protocol is a reliable, open-source, and highly reproducible tool for SST2 immunohistochemistry.
• This quantitative method offers significant advantages over traditional semi-quantitative scoring.
• The DIA provides accurate assessment of SST2 expression, aiding in the management of neuroendocrine tumors.