Expression of somatostatin receptor 2A in medullary thyroid carcinoma is associated with lymph node metastasis

Abstract

Medullary carcinoma (MTC) is an aggressive tumour that derives from the thyroid parafollicular calcitonin-secreting cells (C cells). Lymph node metastasis may occur early in disease pathogenesis and is one of the most important negative prognostic parameters. Surgery is the only curative therapy while chemotherapeutic options are limited. Neuroendocrine differentiated C cells may express somatostatin receptors (SSTR), which have a wide range of biological actions including inhibitory effects on cell survival and angiogenesis and antiproliferative effects on cancer cell lines. Moreover, they are a potential target for various somatostatin analogues. Aim of this study was to analyse the protein expression of SSTR2A and 5 in MTCs with or without the presence of lymph node metastases in correlation with various clinicopathological parameters. This retrospective immunohistochemical analysis included 97 patients with medullary thyroid carcinomas. Protein expression was detected by immunohistochemistry for somatostatin receptors 2A and 5. Various clinicopathological parameters, such as Ki-67 proliferation index or presence of desmoplasia, were included for statistical analysis. SSTR2A protein expression significantly correlated with the presence of lymph node metastases (p = 0.009), locally advanced MTCs staged according to the TNM (p < 0.001) and degree of desmoplasia (p = 0.029). Although SSTR5 protein expression significantly correlated with advanced stages of MTCs (p = 0.023) and degree of desmoplasia (p = 0.020), no correlation was found with the presence of lymph node metastases. Our results provide additional information concerning the aggressiveness of MTCs and reveal that a high SSTR2A and SSTR5 expression might be a poor prognostic feature.

International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature

“…SST 2 was present in 43%–66% of medullary as well as in papillary and follicular thyroid carcinomas ( Papotti et al, 2001 ; Druckenthaner et al, 2007 ; Mussig et al, 2012; Pazaitou-Panayiotou et al, 2012 ; Atkinson et al, 2013 ; Woelfl et al, 2014 ; Herac et al, 2016 ). SST 2 was also detected in a high percentage (>70%) of pheochromocytomas and paragangliomas ( Fischer et al, 2008 ; Lupp et al, 2011 ; Saveanu et al, 2011 ; Elston et al, 2015 ) as well as in 33% of both functioning and nonfunctioning adrenocortical adenomas ( Unger et al, 2008 ).…”

“…21 ) ( Lupp et al, 2011 ; Gabalec et al, 2015 ; Lee et al, 2015 ). Furthermore, the receptor was detected in 38%–57% of medullary and in most of (>75%) papillary and follicular thyroid carcinomas ( Pazaitou-Panayiotou et al, 2012 ; Atkinson et al, 2013 ; Woelfl et al, 2014 ; Herac et al, 2016 ). To a variable extent SST 5 was additionally detected in pheochromocytomas and paragangliomas ( Lupp et al, 2011 ; Elston et al, 2015 ) and in functioning and nonfunctioning adrenocortical adenomas ( Pisarek et al, 2011 ).…”

Peptide receptor radionuclide therapy in patients with medullary thyroid carcinoma: predictors and pitfalls

“…Somatostatin receptor (SSTR) expression has been reported in up to 85% of MTCs, particularly SSTR subtypes 2, 3 and 5 [5][6][7][8], with 49% of MTCs showing expression of the SSTR2a subtype [5]. Somatostatin receptor scintigraphy with 111 In-DTPA-octreotide (Octreoscan®), which has high affinity for SSTR2a, has been reported to show lesional uptake in 57-65% of MTC patients [9][10][11].…”

“…In a retrospective study in 97 patients with MTC, SSTR2a expression was significantly correlated with the presence of lymph node metastasis. However, prognosis was not investigated [8]. In MTC patients, stage IV, 10-year survival rates for SSTR2a negative patients was 43% versus 96% for SSTR2a positive patients [31].…”

Thyroid Nodules in Diagnostic Pathology: From Classic Concepts to Innovations

“…Both CD133 and CD44 are independent factors associated with worse overall survival, while CD44 is also significantly associated with recurrence-free survival [108]. Expression of somatostatin receptors 2A and 5 correlates with advanced stages [109]. Heat shock proteins HSP70, HSP90 and GRP78 are upregulated in MC in comparison with normal thyroid tissues [110].…”