Relevance of somatostatin receptor expression in pancreatic neuroendocrine tumors for treatment with somatostatin analogues

The overexpression of somatostatin receptors (SSTR), a family of G-protein-coupled receptors comprising five distinct subtypes (characterized SSTR1 – 5), mediates the function of somatostatin and characterises neuroendocrine tumors (NETs). Treatment with somatostatin still represents the cornerstone of pancreatic NETs. This approach decreases not only problems related to the secretory activity of the tumors and may relieve symptoms but also decrease the proliferative activity of the tumors. With the advent of new somatostatin analouges targeted to all SSTR subtypes except for SSTR 4 it appears crucial to characterize the expression pattern of SSTR subtypes to define, whether these new analogues may be of additional therapeutic benefit. Thus, the aim of the present study was to investigate the expression pattern of SSTR subtypes in a series of pancreatic NETs.

Using immunohistochemical staining with subtype specific SSTR antibodies (Schmid HA Neuroendocrinology. 2012;95:232) we stained 34 pancreatic neuroendocrine tumors for all SSTR subtypes. Grading of the results was obtained using the Remmele classification (0 = negative to 4 => 80% positivity and intensity 0 = negative to 3 = strong positivity) and forming a product of both subscales for an immunreactivity score (IRS: 0 – 12). These results were correlated to the metastatic status and to markers of proliferation.

Interestingly, none of the tissues staining IRS > 6 showed metastatic behaviour, while all with IRS = 0 did. The pattern of staining for all other subtypes was less characteristic. Interestingly we found a positive correlation of SSTR1 to p53 expression. In conclusion, these descriptive data imply that the SSTR-expression correlates with the behaviour of the pancreatic NET and could be relevant for the treatment response to somatostatin analogues.