Somatostatin Receptors 2A and 5 Are Expressed in Merkel Cell Carcinoma with No Association with Disease Severity

Abstract

Background/Aims: Merkel cell carcinoma (MCC) is a rare high-grade neuroendocrine tumour of the skin. It has been speculated that MCCs express somatostatin receptors (SSTRs), but this has never been assessed in a large series of MCCs. The main aim of this study was to assess the expression of SSTR2A and SSTR5 in MCC tumours. The secondary aims were to assess whether expression of SSTR was associated with the Ki67 proliferative index, Merkel cell polyomavirus (MCPyV) status, clinical characteristics and outcome. Methods: Clinical data and tumours were collected from an ongoing cohort of French patients with MCC. Immunohistochemistry was performed with anti-SSTR2A and anti-SSTR5 monoclonal antibodies, and tumours were classified into 3 groups: ‘no expression', ‘low expression' and ‘moderate expression' using an SSTR staining score. Results: SSTR expression was assessed for 105 MCC tissue samples from 98 patients, and clinical characteristics were available for 87 of them. SSTR expression was consistent between the primary skin tumour and the corresponding metastases for SSTR2A and SSTR5 in 3/7 and 6/7 cases, respectively. SSTR2A and SSTR5 were expressed in 58 cases (59.2%) and in 44 cases (44.9%), respectively. Overall, at least one SSTR was expressed in 75 tumours (76.5%). SSTR expression was not associated with clinical characteristics, Ki67 proliferative index, recurrence-free survival or MCC-specific survival. Expression of SSTR2A was associated with MCPyV status in MCC tumours but not SSTR5. Conclusion: SSTRs were expressed in a high proportion of MCCs, although expression was heterogeneous between tumours and was not associated with disease severity.

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

“…Furthermore, a moderate to strong SST 2 expression was observed in 13% of prostate cancers in general and in 50% of prostate cancers with endocrine differentiation ( Matei et al, 2012 ; Hennigs et al, 2014 ). SST 2 was detected in 59% of Merkel cell carcinomas ( Gardair et al, 2015 ) and in melanomas ( Ardjomand et al, 2003 ; Valsecchi et al, 2013 ). Finally, SST 2 expression in normal exocrine pancreatic tissue is progressively lost during pancreatic ductal adenocarcinoma progression ( Buscail et al, 1996 ; Laklai et al, 2009 ), which participates in tumor aggression, as demonstrated in mouse models of pancreatic cancer combined with SST 2 KO mice ( Chalabi-Dchar et al, 2015 ).…”

Molecular characteristics and potential therapeutic targets in Merkel cell carcinoma

“…Due to the high expression of somatostatin receptors in MCC, lanreotide, a somatostatin analogue, has been used in the treatment of the disease with some responses reported 91. A clinical trial evaluating lanreotide in unresectable and/or metastatic MCC is currently accruing patients 81 91 92…”

Neuroendocrine neoplasms and somatostatin receptor subtypes expression

“…SSTR 2A and SSTR 5 are expressed in 59.2% and in 44.9% of tumors, respectively. Expression of SSTRs is not associated with clinical characteristics, Ki67 proliferative index and survival [84].…”