Expression of the SST receptor 2 in uveal melanoma is not a prognostic marker

Abstract

Introduction Uveal melanoma (UM) cells and neurohormone-producing cells both originate from the neural crest. Somatostatin receptors subtype 2 (SSTR2) are overexpressed in several tumors, often from neuroendocrine origin, and synthetic antagonists like octreotide and octreotate are being used as diagnostic or therapeutic agents. We investigated the SSTR2 expression in UM, and determined whether this expression was related to prognosis of the disease. Materials and methods UM cell lines and fresh primary UM samples were tested for SSTR2 expression by autoradiography (AR) using 125I-Tyr3-octreotate. Furthermore, UM cell lines were analyzed for SSTR2 mRNA expression with quantitative real-time RT-PCR. Results Using AR, cell-surface SSTR2 expression was demonstrated in two UM metastatic cell lines, but no expression was detected in three cell lines derived from primary UM. However, all primary and metastatic UM cell lines showed mRNA expression levels for SSTR2 using quantitative real-time RT-PCR. Only three of 14 primary UM demonstrated moderate SSTR2 expression, and this expression was not significantly associated with tumor-free survival or any tested prognostic factor. Conclusions Based on the rare and low expression of SSTR2 found in primary UM specimens and in UM cell lines, we conclude that SSTR2 is not widely expressed in UM. Furthermore, SSTR2 expression was not associated with tumor-free survival and prognostic factors. Therefore SSTR2 is not suited as prognostic marker or therapeutic target in UM.

Somatostatin receptor scintigraphy in patients with metastatic uveal melanoma

“…At least two previous groups of investigators, although with contradictory results in terms of the prognostic significance, have reported the presence of SSTRs in primary uveal melanoma and cell lines [3,4]. However, to our knowledge, this is the first time that…”

“…Somatostatin receptors (SSTRs) have been shown to be expressed by several different types of tumors, including uveal melanoma [3,4]. However, these previous reports have mainly focused on primary tumors and no previous studies have thoroughly examined SSTR expression in metastases from uveal melanomas.…”

“…At least five subtypes of SSTRs have been described in humans (1, 2A, 2B, 3, 4, and 5) [5,6], and SSTRs 2 and 5 are the ones mainly studied in primary uveal melanoma [3,4]. Commercially available 111 indium-labeled octreotide specifically binds to SSTRs with particular affinity for subtypes 2 and 5, making somatostatin receptor scintigraphy (SRS) an appropriate method for the detection of SSTRs in patients with metastatic uveal melanoma [7].…”

Neuroendocrine Factors in Melanoma Pathogenesis

“…The possible use of somatostatin receptors as molecular targets in anticancer therapy was also explored in uveal melanoma, which expresses mostly SSTR-2 and SSTR-5 [ 214 ]. While the use of somatostatin analogs was proposed as a potential therapy, their impact is undetermined, and there is no consensus regarding the role of SSTRs as prognostic markers in uveal melanoma [ 215 , 216 ].…”

Somatostatin Receptors as Molecular Targets in Human Uveal Melanoma

“…At least five subtypes of SSTRs have been characterized in humans (1, 2A, 2B, 3, 4, and 5), and SSTR-2 and SSTR-5 are the ones mostly studied in human cancers including primary UM. The genes for these subtypes are located on different chromosomes [ 22 , 27 ]. SSTR-2 otherwise splices to generate two isoforms named SSTR-2A and SSTR-2B, which deviate in their C-terminal sequences.…”