Abstract
Abstract: :
Purpose: To investigate the distribution of somatostatin receptor subtypes 2, 3 and 5 in uveal melanomas and its diagnostic and therapeutic value. Methods: Somatostatin receptors (sst) were localized in twenty-five paraffin embedded eyes with uveal melanomas and 6 normal eyes without any pathology using polyclonal antiserum directed to sst 2A, 2B, 3, 5. Antigen expression was evaluated using a semiquantitative method. The expression pattern of sst was correlated with the patients ad vitam prognosis using Kaplan-Meier survival curve. Four patients with a choroidal melanoma underwent octreotide scintigraphy. Six different human melanoma cell lines and one human retinal pigment epithelium cell line were treated with octreotide and vapreotide and a proliferation assay was performed using thymidine 3H. Results: sst 2 was found to be positive in all uveal melanomas, whereas sst 2A was expressed in 15/25 and sst2B in 23/25 uveal melanomas. sst 3 was positive in 7/25 and sst 5 in 13/25 melanomas. The normal human eyes expressed sst 2, 3 and 5 in a very small amount only in the inner and outer plexiform layer of the retina and in the optic nerve. Kaplan-Meier survival curve showed a significant better ad vitam prognosis for patients expressing sst2 in more than 50% of the melanoma cells (13% vs 69%; p<0.02). There was no singificant correlation between sst3 and sst5 concerning survival prognosis. Two out of four patient undergoing octreotide scintigraphy showed a pathologic positive uptake in the diseased eye and additionally also in the liver. Inhibition of cell proliferation could be seen of up to 50% in three out of six melanoma cell lines at a concentration of 10(-4) M octreotide or vapreotide. Conclusion: Somatostatin receptors 2, 3 and 5 are expressed in human uveal melanomas and patients with a high amount of sst2 expression in the melanoma tissue have a better ad vitam prognosis. These findings also have a diagnostic value using octreotide scintigraphy to detect primary and secondary melanomas. Since melanoma cell proliferation assay showed an inhibitory effect of 50% using octreotide, somatostatin analogues might be beneficial in the treatment patients with ocular melanomas.
Keywords: 464 melanoma • 430 imaging/image analysis: clinical • 610 tumors