Endocrine Abstracts (2004) 7 P92

Inhibition of cell proliferation, but lack of antiangiogenic effect on GH-secreting pituitary adenomas treated with Lanreotide

N Garcia de la Torre1, N Sullivan2, V Fazal-Sanderson1, Z Nagy2, JAH Wass1, O Ansorge2 & HE Turner1

1Endocrinology Department. The Oxford Centre for Diabetes, Endocrinology and Metabolism. Churchill Hospital, Headington, Oxford, UK; 2Neuropathology Department, Radcliffe Infirmary, Oxford, UK.

Background: Current available data demonstrate the ability of somatostatin analogues (Ssan) to reduce tumoral size in GH-secreting pituitary adenomas. Somatostatin receptors are present on both tumour cells and vascular endothelium; therefore, potential mechanisms for tumour shrinkage with Ssan include inhibition of cell proliferation, increased cell loss, and inhibition of angiogenesis.

Objective: To assess the mechanisms for tumour shrinkage in GH-secreting pituitary adenomas treated with the long acting Ssan Lanreotide prior to surgery.

Methods: Sixteen patients with previously untreated acromegaly were treated with Lanreotide for 16 weeks before adenomectomy. Twenty-three patients undergoing transsphenoidal surgery and without previous medical treatment were used as controls. The Ki-67 labelling index was used to assess cell proliferation. Cell and nuclear volumes were measured using image analysis. Microvascular density (MVD) was quantified using Chalkley counting of CD34 immunostained vessels. Immunohistochemistry for VEGF was used to assess pro-angiogenic growth factor expression. Serum samples from six pretreated patients were taken at 0, 8 and 16 weeks of treatment with Lanreotide and serum VEGF was determined by ELISA.

Results: The proliferation index was reduced in tumours treated with Lanreotide in comparison with untreated controls (0.59 ± 0.52 % versus 1.23 ± 0.55%, P= 0.0008). The cell and nuclear volumes showed a trend to decrease with Lanreotide treatment, although the differences did not reach statistical significance (148 ± 34.65 versus 173 ± 57.92, P= 0.09, and 47.52 ± 11.06 versus 55.69 ± 16.63 square microns, P= 0.07, respectively). MVD and VEGF expression were not different between groups. Circulating levels of VEGF were not different pre-treatment, and after 8 and 16 weeks on Lanreotide.

Conclusions: The antitumoral effects of Lanreotide on GH-secreting pituitary adenomas appear to be associated with inhibition of cell proliferation and probably cell shrinkage. An antiangiogenic effect is unlikely to play a key role in GH-secreting adenomas shrinkage.

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