Immunohistochemical Expression of Somatostatin Receptor Subtypes in a Panel of Neuroendocrine Neoplasias

Neuroendocrine neoplasias (NENs) are known to express somatostatin receptors (SSTRs) 1-5, which are G-protein-coupled cell membrane receptors. Somatostatin receptor imaging and therapy utilizes the SSTR expression. Synthetic somatostatin analogs with radioligands are used to detect primary tumors, metastases, and recurrent disease. Receptor analogs are also used for treating NENs. Furthermore, commercially available SSTR antibodies can be used for the immunohistochemical (IHC) detection of SSTRs. We investigated different SSTR antibody clones applying diverse IHC protocol settings to identify reliable clones and feasible protocols for NENs. A tissue microarray including NENs from 12 different primary sites were stained. Only UMB clones were able to localize SSTR on the cell membranes of NENs. SSTR2 (UMB1) emerged as the most common subtype followed by SSTR5 (UMB4) and SSTR1 (UMB7). SSTR3 (UMB5) expression was mainly cytoplasmic. Yet, SSTR4 expression was weak and located primarily in the cytoplasm. Thus, appropriate IHC protocols, including proper positive and negative controls, represent requirements for high-quality NEN diagnostics and for planning personalized therapy.Peer reviewe

Immunohistochemical somatostatin receptor expression in insulinomas

Abstract Insulinomas are rare pancreatic neuroendocrine tumours. Most patients can be cured with surgery, but patients with a metastatic disease show impaired survival. The aim of this study was to evaluate somatostatin receptor (SSTR) 1‐5 expression in insulinomas and to correlate the expression profile with clinicopathological variables and with patient outcome. This retrospective study involved 52 insulinoma patients. After histological re-evaluation, formalin-fixed paraffin-embedded tissue samples were processed into tissue microarrays and stained immunohistochemically with monoclonal SSTR1‐5 antibodies. All the 52 tumours (49 non-metastatic, 3 metastatic) expressed at least one SSTR subtype. SSTR2 was expressed most frequently (71%), followed by SSTR3 (33%), SSTR1 (27%), SSTR5 (6%) and SSTR4 (0%). SSTR3 expression was associated with a larger tumour size (median diameter 19 mm vs. 13 mm, p = 0.043), and SSTR3 and SSTR5 expression were associated with impaired overall survival [HR 3.532 (95% CI 1.106‐11,277), p = 0.033, and HR 6.805 (95% CI 1.364‐33.955), p = 0.019 respectively]. Most insulinomas express SSTR2, which may be utilized in diagnostic imaging, and in planning individualized treatment strategies for insulinoma patients. Further studies are needed to clarify the association between SSTR profile and overall survival