The distribution of the
sst2A receptor was investigated, using immunohistochemistry, with the specific antipeptide antibody R2-88, in a total of 120
tumors of the nervous and the neuroendocrine systems, including small-cell lung
carcinomas,
medulloblastomas,
neuroblastomas,
pheochromocytomas, and
paragangliomas. The great majority of the
tumor samples, frozen or
formalin-fixed, showed a positive immunohistochemical staining with R2-88, and an excellent correlation with receptor autoradiography using 125I[Tyr3]-
octreotide. Whereas small-cell lung
carcinomas and
medulloblastomas had a predominantly plasma membrane staining,
pheochromocytomas and
neuroblastomas had variable ratios of cell surface and intracellular staining. Strikingly, a preferentially cytoplasmic staining was seen in
tumors with a high level of
somatostatin gene expression, whereas a more plasma membranous staining was seen in
tumors lacking
somatostatin messenger RNA. Specificity of both the plasma membrane and the cytoplasmic staining pattern was confirmed in immunoblots, which showed the immunoreactive receptor migrating as a characteristic 70-kDa broad band. In both immunohistochemical and immunoblotting experiments, staining was abolished by antibody blockade with 100 nM
antigen peptide. These results describe, for the first time, the localization of the
sst2A receptor protein in human small-cell lung
carcinomas,
medulloblastomas,
neuroblastomas, and
paragangliomas. Moreover, it is the first report investigating possible causes for distinct subcellular localizations of sst2A in human tissues. We show that the subcellular distribution of the receptor may be dependent on the surrounding
somatostatin concentration, consistent with both the known effect of
somatostatin to cause
sst2A receptor internalization and an autocrine regulation of
tumors by the
peptide they produce. Moreover, our demonstration that the
sst2A receptor can be identified in this group of
tumors using simple immunohistochemical methods in
formalin-fixed,
paraffin-embedded material opens numerous diagnostic, therapeutic, and prognostic opportunities.