Immunohistochemical Determination of Somatostatin Receptor Subtypes 1, 2A, 3, 4, and 5 in Various Adrenal Tumors

Unger, Nicole; Serdiuk, I; Sheu, Sien‐Yi; Walz, M. K.; Schulz, Stefan; Schmid, K. W.; Mann, Klaus; Petersenn, Stephan

doi:10.1081/erc-200044161

Cited by 28 publications

(39 citation statements)

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“…Using immunohistochemical methods, Mundschenk et al [13] found the presence of SSTR 3 in 90%, SSTR 2A -in 25%, SSTR 4 -in 10%, SSTR 5 -in 15% and SSTR 1 -in 8% of studied pheochromocytomas. Unger et al [17] demonstrated the expression of SSTR 1, 2A and 5 in 1/3 of the studied pheochromocytomas with 30% positive staining cells whereas SSTR 3 occurred in all of the cases and the percentage of cells with positive staining was 60%.…”

Section: Discussionmentioning

confidence: 99%

“…Unger et al [17] Abbreviations: mem -membranous localization; cytopl -cytoplasmatic localization; strong staining (+++), moderate staining (++), weak staining (+) and pale staining (+/-).…”

Section: Discussionmentioning

confidence: 99%

“…Despite the fact that the adrenal gland has long been known as the target organ for SST and SST receptors have been found there in physiological conditions [13,14] data concerning the occurrence of SSTR in human adrenal gland tumors are still scarce and often conflicting [15][16][17][18]. Somatostatin analogs are not routinely used in treatment of adrenal tumors so far.…”

Section: Introductionmentioning

confidence: 99%

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Somatostatin receptors in human adrenal gland tumors--immunohistochemical study.

Pisarek

Stępień²,

Kubiak³

et al. 2008

Folia Histochem Cytobiol.

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Section: Discussionmentioning

confidence: 99%

“…Unger et al [17] Abbreviations: mem -membranous localization; cytopl -cytoplasmatic localization; strong staining (+++), moderate staining (++), weak staining (+) and pale staining (+/-).…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Somatostatin receptors in human adrenal gland tumors--immunohistochemical study.

Pisarek

Stępień²,

Kubiak³

et al. 2008

Folia Histochem Cytobiol.

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“…The catecholamine-producing and -secreting tumor pheochromocytoma has been shown to express SS (Reubi et al 1992c) and more than one SSTR receptor both at mRNA and protein level (Reubi et al 1992c, Kubota et al 1994, Mundschenk et al 2003, Kolby et al 2006, being the subtypes 1-3 the most represented (Hofland & Lamberts 2003, Unger et al 2004. Similarly, in vivo and in vitro studies on medullary thyroid carcinomas detected the presence of all sst subtypes, except sst 4 , and showed a clear positivity for SS, indicating that possible autocrine/ paracrine circuits may be active in this tumor (Pacini et al 1991, Kwekkeboom et al 1993, Mato et al 1998, Papotti et al 2001b, Zatelli et al 2006).…”

Section: Sstr Expression In Endocrine Tumorsmentioning

confidence: 99%

The role of somatostatin and dopamine D2 receptors in endocrine tumors

Gatto¹,

Hofland²

2011

Endocrine-Related Cancer

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Somatostatin (SS) and dopamine (DA) receptors have been highlighted as two critical regulators in the negative control of hormonal secretion in a wide group of human endocrine tumors. Both families of receptors belong to the superfamily of G protein-coupled receptors and share a number of structural and functional characteristics. Because of the generally reported high expression of somatostatin receptors (SSTRs) in neuroendocrine tumors (NET), somatostatin analogs (SSA) have a pronounced role in the medical therapy for this class of tumors, especially pituitary adenomas and well-differentiated gastroenteropancreatic NET (GEP NET). Moreover, NET express not only SSTR but also frequently dopamine receptors (DRs), and DA agonists targeting the D 2 receptor (D 2 ) have been demonstrated to be effective in controlling hormone secretion and cell proliferation in in vivo and in vitro studies. The treatment with SSAs combined with DA agonists has already been demonstrated efficacious in a subgroup of patients with GH-secreting pituitary adenomas and few reported cases of carcinoids. The recent availability of new selective and universal SSA and DA agonists, as well as the chimeric SS/DA compounds, may shed new light on the potential role of SSTR and D 2 as combined targets for biotherapy in NET. This review provides an overview of the latest studies evaluating the expression of SSTR and DR in NET, focusing on their co-expression and the possible clinical implications of such co-expression. Moreover, the most recent insights in SSTR and D 2 pathophysiology and the future perspectives for treatment with SSA, DA agonists, and SS/DA chimeric compounds are discussed.

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“…The various effects of somatostatin and its analogs are mediated through five-membrane G protein-coupled receptors: somatostatin receptor subtypes 1-5 (sst [1][2][3][4][5] ). The presence of sst in PCC/PGL has been demonstrated by ligand binding studies , Reubi & Laissue 1995, Reubi et al 2001, by immunohistochemistry (Mundschenk et al 2003, de Herder & Hofland 2004, Unger et al 2004, and more recently by reverse transcriptase (RT)-PCR (Ueberberg et al 2005, Kolby et al 2006, Binderup et al 2008. However, the current SRIF analogs, directed mainly to sst 2 , have little if any efficacy on catecholamine secretion of PCC (Invitti et al 1993, Kopf et al 1997, Lamarre-Cliche et al 2002, or on tumoral growth of PGL (Tonyukuk et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Expression of somatostatin receptors, dopamine D2 receptors, noradrenaline transporters, and vesicular monoamine transporters in 52 pheochromocytomas and paragangliomas

Saveanu¹,

Mureşan²,

Micco³

et al. 2011

Endocrine Related Cancer

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While somatostatin receptors (sst), through somatostatin-radiolabeled analogs, are used, mainly in second line, in the diagnosis and treatment of pheochromocytomas (PCC) and paragangliomas (PGL), the clinical significance of dopamine receptor subtype 2 (D 2 ) in PCC/PGL is unknown. Indeed, radiolabeled dopamine (DA) analogs such as fluorine 18 ( 18 F)-DA, used for positron emission tomography in PCC localization, are mainly correlated to the presence of noradrenaline transporter (NAT) and vesicular monoamine transporters (VMAT) but not to D 2 . The aim of this study was to quantitate D 2 and sst expression in 52 PCC/PGL and to compare it with that of 35 gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Quantitative RT-PCR of sst 1-3 and sst 5 , D 2 , NAT, VMAT1/2 was performed in all tumors, while immunohistochemistry analysis of sst 2 and D 2 was performed in seven tumors. D 2 mRNA was expressed in all PCC/PGL. Mean expression was significantly higher in PCC/PGL than in GEP-NETs (4.8 vs 0.5 copy/copy b-glucuronidase (Gus)). sst 2 and sst 1 were expressed in most PCC/PGL, with sst 2 -dominant expression (mean mRNA: 1.6 vs 0.4 copy/copy b-Gus). sst 2 expression level was similar to that of GEP-NETs, whereas sst 5 expression level was significantly lower (0.12 vs 0.78 copy/copy b-Gus). Our study evidenced strong D 2 mRNA expression in PCC and for the first time in PGL. PCC/PGL express sst 2 mRNA at levels similar to those of GEP-NETs. New drugs can target ssts and D 2 more efficiently than current somatostatin analogs. Moreover, transporters like NAT and VMAT1/2, could be co-targeted with sst, as a basis of new radionuclide compounds in the imaging and treatment of these tumors.

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Immunohistochemical Determination of Somatostatin Receptor Subtypes 1, 2A, 3, 4, and 5 in Various Adrenal Tumors

Cited by 28 publications

References 2 publications

Somatostatin receptors in human adrenal gland tumors--immunohistochemical study.

Somatostatin receptors in human adrenal gland tumors--immunohistochemical study.

The role of somatostatin and dopamine D2 receptors in endocrine tumors

Expression of somatostatin receptors, dopamine D2 receptors, noradrenaline transporters, and vesicular monoamine transporters in 52 pheochromocytomas and paragangliomas

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