Neuroendocrine neoplasms and somatostatin receptor subtypes expression

Abstract

Neuroendocrine neoplasms (NENs) show wide spectrum of clinical course -from benign biological potential to recurrences and rapidly progressive disease. Somatostatin analogs that bind to somatostatin receptor are part of the therapy; detection and evaluation of activation of somatostatin receptor subtypes are part of the process of new therapy induction. When using RT-PCR method and immunohistochemistry, it is possible to detect more than two SSTR subtypes in majority or all neuroendocrine neoplasms regardless tumor origin. Generally with some exceptions, from the viewpoint of tumor grade -apart the site of origin, there is a tendency to decrease the percentage of SSTRs expression; 100% (G1, 2)-85.7% (G3) for SSTR 1; 81.8% (G1, 2)-61.9% (G3) for SSTR 2; 54.5% (G1, 2)-52.4% (G3) for SSTR 3; 9% (G1, 2)-4.8% (G3) for SSTR 5. Different studies indicate significant differences in the expression of SSTR 1 and 2A and 2B between NEC G3 small cell type and non-small cell type.Further research on SSTRs expression in NEN could serve as base to development and improvement of somatostatin analogs' pharmacotherapy in patients with unsatisfactory course.

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

“…The SSTR expression profiles vary according to the NEN origin, differentiation, and tumor grade, an observation supported in our studies. [10][11][12]22 Cytoplasmic staining has been accepted as sufficiently specific in previous reports on SSTR expressions, although we considered only membranous positivity as the correct and reliable staining pattern for SSTRs, 23 even though we also scored the cytoplasmic staining. Furthermore, SSTR2 (UMB1) was the most frequently detected membranous receptor subtype followed by SSTR5 (UMB4) and SSTR1 (UMB7).…”

“…[10][11][12] The expression profile and coexpression of various SSTR subtypes differ according to the NEN location, histological differentiation, and tumor grade. 11,12 Somatostatin radioligands are used for tumor imaging, playing a major role in localizing primary tumors and in the identification of metastases. Moreover, somatostatin analog-based therapies of NENs utilize the expression of SSTRs.…”

The radiosensitizer Onalespib increases complete remission in 177Lu-DOTATATE-treated mice bearing neuroendocrine tumor xenografts

“…Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00259-019-04673-1) contains supplementary material, which is available to authorized users. SSTRs are overexpressed in a variety of cancers where the highest abundance of around 80% is found in welldifferentiated NETs originating from the GI tract and pancreas [4]. The SSTRs can be targeted with somatostatin analogues conjugated to a therapeutic radionuclide [5].…”

Practical management of toxicities associated with targeted therapies for advanced gastroenteropancreatic neuroendocrine tumors

“…Most NETs express several SSTRs at high levels, with SSTR2 acting as the predominant subtype [ 6 ]. However expression levels and predominant subtype can vary between NET tumor types [ 7 ]. Somatostatin is a natural polypeptide playing an inhibitory role in pituitary, pancreatic and gastrointestinal (GI) hormone secretion, through its high affinity binding to all five SSTR subtypes (SSTR1-5).…”