Differential somatostatin receptor (SSTR) 1–5 expression and downstream effectors in histologic subtypes of growth hormone pituitary tumors

Abstract

Purpose The aim of this study was to examine whether differential expression of somatostatin receptors (SSTR) 1-5 and downstream effectors are different in densely (DG) and sparsely (SG) granulated histological growth hormone (GH) pituitary tumor subtypes. Methods The study included 33 acromegalic patients with 23 DG and 10 SG tumors. SSTR1-5 were measured by qPCR and immunoblotting. Signaling candidates downstream of SSTR2 were also assessed. Results SSTR2 mRNA and protein levels were significantly higher in DG compared to SG tumors. Downstream of SSTR2, p27kip1 was decreased (2.6-fold) in SG compared to DG tumors, suggesting a potential mechanism of SSA resistance in SG tumors with intact SSTR2 expression. Re-expression of E-cadherin in GH pituitary cell increased p27kip1 levels. Conclusions Histological subtyping correlated with SSTR2, E cadherin and p27 kip protein levels and these may serve as useful biomarkers in GH tumors to predict behavior and response to therapy with SSA.

Association between dopamine and somatostatin receptor expression and pharmacological response to somatostatin analogues in acromegaly

“…SSTR5 was the predominant SSTR subtype detected, followed by SSTR2, SSTR3 and SSTR1. These findings are in agreement with previous studies using similar methodological approaches . In line with this, Casarini et al .…”

E‐cadherin expression is associated with somatostatin analogue response in acromegaly

“…As previously reported, [21][22][23][24][25] we found E-cadherin expression levels are associated with GH-producing tumour histological subtypes. SGSAs tumours displayed low E-cadherin levels while DGSAs tumour showed high E-cadherin levels.…”

“…[21][22][23][24] To confirm this notion in our series of 55 tumours, granulation pattern was examined. [21][22][23][24] To confirm this notion in our series of 55 tumours, granulation pattern was examined.…”

“…C, Comparison of IGF1 per cent reduction after 6 mo of SSAs treatment with the different histological subtypes of GH-producing tumours. 22,40 Finally, while the relationship between E-cadherin and SSTR5 expression is poorly know, it is worth noting that the expression of SSTR5 and some of its truncated variants comprises the only known markers among SSTRs for worse patient response to SSAs. Mean and SEM are also displayed.…”

“…Thus, whereas high E-cadherin expression levels are found in densely granulated somatotroph adenomas (DGSAs) tumours, low or absent E-cadherin expression is observed in sparsely granulated somatotroph adenomas (SGSAs). [21][22][23][24][25] Of note, the granulation pattern of GH-producing tumours is considered a histological marker of response to SSAs treatment with SG somatotropinomas presenting a worse response to SSAs treatment. 26 Despite all these findings, the potential association between E-cadherin expression and SSAs response in GH-producing tumours has been barely studied to date.…”