Expression of somatostatin receptors in uveal melanomas
Abstract
PURPOSE: To investigate the distribution of somatostatin receptor (SSR) subtypes 2, 3, and 5 in uveal melanomas and their diagnostic and possible therapeutic value.
METHODS: SSRs were investigated in 25 paraffin-embedded eyes with uveal melanomas and in 6 normal eyes without any disease, by using polyclonal antiserum directed to SSR2A, -2B, -3, and -5. Antigen expression was evaluated by a semiquantitative method. The expression pattern of SSR was correlated with the patients' ad vitam prognosis by use of the Kaplan-Meier survival curve. Six different human melanoma cell lines were incubated with octreotide and vapreotide, and a proliferation assay was performed by determining [(3)H]-TdR uptake. [111-Indium-DTPA-D-Phe1]-octreotide scintigraphy was performed in the eyes of four patients with known uveal melanomas.
RESULTS: All uveal melanomas were positive for SSR2. SSR2A was expressed in 15 of 25, SSR2B in 23 of 25, SSR3 in 7 of 25, and SSR5 in 13 of 25 uveal melanomas. A Kaplan-Meier survival curve showed a significantly better ad vitam prognosis for patients with tumors expressing high levels of SSR2. Cell proliferation was inhibited up to 36% +/- 6% in three of six melanoma cell lines at a concentration of 10(-4) M octreotide or vapreotide. Eyes of two patients with uveal melanomas showed positive uptake of [111-Indium-DTPA-D-Phe1]-octreotide.
CONCLUSIONS: SSR2, -3, and -5 are expressed in human uveal melanomas and patients with a high amount of SSR2 in the melanoma tissue have a better ad vitam prognosis. Because a melanoma cell proliferation assay showed an inhibitory effect of up to 36% +/- 6% using octreotide or vapreotide, somatostatin analogues may be beneficial in the treatment of patients with ocular melanomas.