Correlation of in Vitro and in Vivo Somatotropic Adenoma Responsiveness to Somatostatin Analogs and Dopamine Agonists with Immunohistochemical Evaluation of Somatostatin and Dopamine Receptors and Electron Microscopy

Abstract

Twenty-four pituitary adenomas from acromegalic patients (13 females, 11 males; age range 19-65 yr) were characterized for somatostatin receptor subtype 2A (sst(2A)), dopamine D(2) receptor (D(2)R), GH, and prolactin (PRL) expression by immunohistochemistry, and results correlated with the in vitro and in vivo hormone responses to octreotide and quinagolide. In nine cases, GH and PRL content was further studied by immunoelectron microscopy. Immunoreactivity was semiquantitatively scored as 2 (>50% stained cells), 1 (10-50% stained cells), and 0 (<10% stained cells). Sst(2A) was scored as 2 in 13 cases, 1 in 10, and 0 in one; D(2)R was scored as 2 in 13 cases, 1 in nine, and 0 in 2; GH was 2 in 15 cases and 1 in nine; PRL was 2 in six cases, 1 in 13, and 0 in 5. Sst(2A) was positively correlated with in vitro (P = 0.003) and in vivo (P = 0.006) percent GH suppression by octreotide and with the chronic suppression of IGF-I by somatostatin analogs (P =0.008). D(2)R was positively correlated with in vitro percent GH (P =0.000) and PRL (P =0.005) suppression by quinagolide. Electron microscopy revealed two pure somatotroph adenomas, five somatomammotrophs with a variable coexpression of GH and PRL in the same cells, and two tumors consisting of mixed cell types, which were less sensitive to quinagolide and octreotide. Sst(2A) and D(2)R are frequently coexpressed in adenomas from acromegalic patients, and immunohistochemistry may be helpful in characterizing receptor expression in pituitary adenomas to select patients responsive to different treatments.