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Immunohistochemical Detection of Somatostatin Receptor Subtypes sst1 and sst2A in Human Somatostatin Receptor Positive Tumors

Department of Internal Medicine III (L.J.H., P.M.K., J.Z., S.W.J.L.) and Pathology (F.H., R.R.K.), Erasmus University Rotterdam, Rotterdam 3015 GD, The Netherlands, and Department of Integrative Biology and Pharmacology (A.S., Q.L.), University of Texas, Houston, Texas 77225

Address all correspondence and requests for reprints to: L.J. Hofland, Ph.D., Department of Internal Medicine III, University Hospital Dijkzigt, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. E-mail: hofland{at}inw3.azr.nl

Although in situ hybridization has been used to examine the distribution of messenger RNA for somatostatin receptor subtypes (sst) in human tumors, the cellular localization of sst₁ and sst_2A receptors has not been reported. In this study, we describe the cellular localization of human sst₁ and sst_2A receptor proteins in both cryostat- and paraffin-embedded sections of 25 human tumor tissues using two recently developed polyclonal antibodies. Six somatostatin (SS) receptor (SSR) positive tumors (two gastrinomas, three carcinoids, one pheochromocytoma) and one SSR negative tumor (renal cell carcinoma), selected by positive and negative SSR autoradiography, respectively, were studied by both immunohistochemistry and Western blot analysis. The six SSR positive tumors expressed sst_2A, while 4 of 5 expressed sst₁ as well. The SSR negative tumor did not express either sst₁ or sst_2A. Western blot analysis of wheat germ agglutinin purified membrane proteins confirmed the presence of the sst₁ and sst_2A glycosylated receptors. The paraffin-embedded sections gave best information with respect to the subcellular localization. Sst₁ immunoreactivity was observed both on the membrane and in the cytoplasm, while sst_2A showed predominantly membrane-associated immunoreactivity. This subcellular distribution of sst₁ or sst_2A receptors was confirmed in paraffin-embedded sections of 8 additional intestinal carcinoids, 5 gastrinomas and 5 pheochromocytomas. Sst₁ receptors were detected in 7 out of 8 carcinoids, in all gastrinomas, and in 4 out of 5 pheochromocytomas, while 6 out of 8 carcinoids, all gastrinomas, and 3 out of 5 pheochromocytomas expressed sst_2A receptors. In conclusion, sst₁ and sst_2A receptors show a differential subcellular localization in human SSR positive tumors. The use of SSR subtype selective antibodies to detect the subcellular distribution of SSR subtypes in individual tumor cells is an important step forward to understand more about the pathophysiological role of the different SSR subtypes in human tumors.

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