Expression of somatostatin receptors in uveal melanomas

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. Conclusion. 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.