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Submitted on September 5, 2007
Accepted on January 3, 2008
Interdisziplinäres Stoffwechsel-Centrum: Endokrinologie, Diabetes und Stoffwechsel, Med. Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Germany; Department of Neuropathology, Klinikum der Friedrich-Schiller-Universität Jena, Germany; Institute of Pathology, Marien Krankenhaus, Hamburg, Germany; Department of Neurosurgery, Friedrich-Alexander University, Erlangen-Nürnberg, Germany; Division of Endocrinology, University of Duisburg-Essen, Germany; Department of Pharmacology and Toxicology, Bayerische Julius-Maximilians-Universität, Würzburg, Germany
* To whom correspondence should be addressed. E-mail: stefan.schulz{at}toxi.uni-wuerzburg.de.
Objective. The somatostatin analog octreotide preferentially binds to somatostatin receptor 2A (sst2A) and to a lesser extent to somatostatin receptor 5 (sst5). Although sst2A and sst5 mRNAs are consistently expressed in GH-secreting adenomas, octreotide controls GH secretion only in 65% of acromegalic patients. Hence, we investigated the immunocytochemical expression of sst in a large group of somatotroph tumors.
Methods. Acromegalic patients, cared for in a university referral centre, were either operated on without pre-treatment (Group A, N=14) or pre-treated with octreotide [median (min-max): dose 1250 (300–1500) µg/d for 5.6 (3–9) months] before surgery (Group B, N=20). In group B octreotide reduced GH-secretion by more than 50% in 14 (70%) patients (GH-responders). Six patients with less than 50% GH suppression were considered GH non-responders. We used a panel of extensively characterized antibodies to determine the immunocytochemical sst status in somatotroph adenomas and compared their expression between the groups.
Results. All group A tumors demonstrated immunoreactive sst2A and all but one had sst5. A similar pattern was found in the GH-responders of group B. In contrast, none of the GH non-responders exhibited detectable sst2A (sst2A: GH-responders vs. GH non-responders, p<0.0001), whereas sst5 was found in 70%. Sst1 and sst3 were detected in 85% and 24% of all cases, independent of previous octreotide treatment.
Conclusions. Our findings suggest that octreotide-resistance in GH-secreting adenomas occurs due to a selective loss of sst2A. The persistent expression of sst1 and sst5 receptors suggests these tumors are potential targets for pan-somatostatin analogs.
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