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This version published online on January 22, 2008
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-1358
A more recent version of this article appeared on April 1, 2008
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Submitted on June 19, 2007
Accepted on January 15, 2008

Correlation of in vitro and in vivo somatotrophic adenoma responsiveness to somatostatin analogs and dopamine agonists with immunohistochemical evaluation of somatostatin and dopamine receptors and electron microscopy

Diego Ferone*, Wouter W de Herder, Rosario Pivonello, Johan M Kros, Peter M van Koetsveld, Ton de Jong, Francesco Minuto, Annamaria Colao, Steven WJ Lamberts, and Leo J Hofland

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, Rotterdam, The Netherlands; Department of Molecular & Clinical Endocrinology and Oncology (R.P., A.C.) "Federico II" University, Naples, Italy; Department of Endocrinological & Medical Sciences and Center of Excellence for Biomedical Research (F.M.), University of Genova, Italy

* To whom correspondence should be addressed. E-mail: ferone{at}unige.it.

Objective and Patients: 24 pituitary adenomas from acromegalic patients (13 f, 11 m; age range 19–65 yrs) were characterized for somatostatin receptor subtype 2A (sst2A), dopamine D2 receptor (D2R), GH and PRL expression by immunohistochemistry, and results correlated with the in vitro and in vivo hormone responses to octreotide and quinagolide. In 9 cases, GH and PRL content was further studied by immuno-electron microscopy (EM).

Results: Immunoreactivity was semiquantitatively scored as 2 (>50% stained cells), 1 (10% to 50% stained cells), 0 (<10% stained cells). Sst2A was scored as 2 in 13 cases, 1 in 10, and 0 in 1; D2R was scored as 2 in 13 cases, 1 in 9, and 0 in 2; GH was 2 in 15 cases and 1 in 9, PRL was 2 in 6 cases, 1 in 13, 0 in 5. Sst2A 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. EM revealed 2 pure somatotroph adenomas, 5 somatomammotrophs with a variable co-expression of GH and PRL in the same cells, and 2 tumors consisting of mixed cell types which resulted less sensitive to quinagolide and octreotide.

Conclusion: Sst2A and D2R are frequently co-expressed in adenomas from acromegalic patients, and immunohistochemistry may be helpful in characterizing receptor expression in pituitary adenomas, in order to select patients responsive to different treatments.


Key words: pituitary • acromegaly • somatostatin receptors • dopamine receptors • octreotide • quinagolide • immunohistochemistry • immuno electron microscopy




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[Abstract] [Full Text] [PDF]




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