Endocrine Abstracts (2006) 11 OC36

Somatostatin analogues in the treatment of acromegaly: correlation between somatostatin receptor subtype expression levels and clinical response

S Petersenn1, A Redmann1, DK Luedecke2 & K Mann1

1Division of Endocrinology, University of Essen, Essen, Germany; 2Department of Neurosurgery, University of Hamburg, Hamburg, Germany.

Aim: Somatostatin mediates its effects via five known receptor subtypes sst1-sst5. The somatostatin analogue octreotide, which binds preferentially to sst2 and to a lesser extent to sst3 and sst5, may be used prior to surgery of GH-secreting tumors. To investigate the variable response rates of such treatment, we analyzed sst expression levels in tumor tissue.

Methods: 44 patients with acromegaly (20m, 24f, 48.7+/−1.8 years, GH 43.7+/−1.8 ng/ml, IGF-1 1001+/−56 ng/ml) underwent pre-operative treatment with octreotide for a period of 7.3+/−0.5 (3–18) months. Clinical response was evaluated by determination of mean GH levels and IGF-1 levels, as well as tumor size by MRI. After surgery, RNA samples obtained from snap-frozen tumor tissue underwent one-step real-time RT-PCR using subtype specific primers. Sst mRNA copy numbers were calculated by parallel amplification of specific cDNAs.

Results: During treatment with octreotide, GH and IGF-1 levels were lowered to 28.2+/−8.0% and 57.0+/−3.4%, respectively. GH<2.5 ng/ml and normal IGF-1 were obtained in 34.1% and 43.2% of patients, tumor shrinkage >20% was observed in 38.6%. In tumors, relevant expression of sst1, sst2, sst3, sst4, and sst5 was observed in 88.6%, 97.7%, 43.2%, 15.9%, and 97.7%, with a wide range of variation. Expression levels of sst2 were significantly higher in patients with pre-operative normalization of IGF-1 (131+/−21 vs. 54+/−11 copies/ng RNA, P<0.005), without any differences for the other ssts. ROC analysis suggested an optimal threshold of 70 sst2 copies/ng RNA with a sensitivity of 74% and a specificity of 76% for normalization of IGF-1. No significant differences in expression levels for any sst were observed between tumors with and without tumor shrinkage.

Conclusions: Quantitative real-time RT-PCR is a precise method to establish clinically relevant information by investigation of tissue samples. Sst2 is the relevant receptor eliciting the biochemical response to octreotide. Analysis of sst2 expression levels may be useful to predict response to treatment with octreotide.

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