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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

Departments of Internal Medicine (D.F., W.W.d.H., P.M.v.K., S.W.J.L., L.J.H.) and Pathology (J.M.K., T.d.J.), Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands; Department of Molecular and Clinical Endocrinology and Oncology (R.P., A.C.) "Federico II" University, 80131 Naples, Italy; and Department of Endocrinological and Medical Sciences and Center of Excellence for Biomedical Research (F.M.), University of Genova, 16132 Genova, Italy

Address all correspondence and requests for reprints to: Diego Ferone, M.D., Ph.D., Department of Endocrinology and Medical Sciences, University of Genova, Viale Benedetto XV, 6, 16132 Genova, Italy. E-mail: ferone{at}unige.it.

Objective and Patients: 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 D₂ receptor (D₂R), 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.

Results: 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; D₂R 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). D₂R 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.

Conclusion: Sst_2A and D₂R 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.