Somatostatin receptors in normal and acromegalic somatotroph cells: the U-turn of the clinician to immunohistochemistry report – a review

Abstract

This is a narrative review of literature introducing somatostatin receptors (SSTRs) as part of understanding the somatotroph cells since they are positive in normal cells but also in tumoral cells as seen in somatotropinoma, a growth hormone (GH)-producing neoplasia, which causes acromegaly. They are five subtypes of SSTRs (1 to 5), which are immunohistochemically positive in different proportions in somatotropinomas. SSTR types 2 and 5 are most frequent in GH-secreting adenomas and they are both targeted by medical therapy with somatostatin analogues (SSTAs) like first generation Octreotide and Lanreotide (mainly targeting SSTR2) and second generation Pasireotide (with highest affinity for SSTR5), thus heterogeneous SSTRs configuration into the tumor explains different pattern of response to treatment and it might predict it once the SSTRs immunostaining is performed. Monoclonal antibodies are used for immunohistochemical detection of SSTRs; currently, a lack of standardization is presented, and scoring systems, such as Volante, H-score or human epidermal growth factor receptor 2 (HER2)score, are applied. Immunoreactive markers like SSTRs are the U-turn in clinical practice regarding somatotropinomas since the configuration of subtypes 2 and 5 explains the responsiveness to medical therapy like SSTA. Further achievement of disease control is imperiously necessary because acromegaly has an increased rate of morbidity and mortality.

Immunohistochemical evaluation of biomarkers with predictive role in acromegaly: a literature review

“…The main difference between the patients group included in this study and the other ones mentioned earlier was that most included patients were partially responsive to fg-SRLs, whereas in Iacovazzo et al study only fg-SRLs resistant patients were evaluated for Pasireotide response [ 38 , 40 ]. All things considered, it can be suggested that routine evaluation for IHC expression of SSTRs may be beneficial to facilitate the switch to “targeted therapy”, by subcategorizing patients into fg-SRLs responsive and resistant, for which Pasireotide could be a reasonable first-line therapy choice [ 41 ]. While the evidence for the predictive role of SSTR-2 in SRLs response appears to be clear, results on SSTR-5 are still contradicting, probably also due to the limited evidence and heterogenous patients’ populations used in different studies [ 20 ].…”