Pasireotide (SOM230), a somatostatin (SST) analogue targeting multiple SST receptors, is effective in reducing urinary free cortisol in patients with Cushing disease (CD), due to inoperable or recurrent ACTH secreting pituitary adenomas. The efficacy of SOM230 seems to be dependent on the presence of appropriate SSTRs, mainly SSTR2 and 5, on the membrane of tumor cells. Polyclonal antibodies available up to now recognizing cellular intracellular sites of receptors and their recycling products are of limited performance in paraffin-embedded tissues. Aim of this study was to evaluate by immunohistochemistry the expression of SSTR 2 and 5 on ACTH-secreting cells using new MoAbs against the sst-binding domain. We used paraffined tissue sections from 45 ACTH-secreting pituitary adenomas. A standard streptavidin-biotin-labeled peroxidase immunostaining was performed. Negative controls were performed with non immune serum. The degree of immunopositivity was evaluated semi-quantitatively according to an arbitrary scale.
Results: SSTR2 and SSTR5 were found respectively, in 80% and in 100% of adenoma samples. The immunostaining intensity score was higher for SSTR5 (high/medium-high) than for SSTR2 (low/medium-low). Negative control reactions were performed by incubation with a pre-immune serum. The specificity of the reactions was tested by pre-adsorption of antibodies with their immunospecific peptides.
Conclusion: SSTR5 was present in all of ACTH-secreting pituitary adenomas examined, and was associated with SSTR2 positivity in a majority of them. An higher immunostaining score was found for SSTR5 than for SSTR2. These data demonstrate that Y-SSTR2 and 5 MoAbs are able to detect SSTRs on paraffin embedded histological sections. Finally, our findings support the use of SOM230 in CD due to resistant/recurrent ACTH-secreting pituitary tumors.
30 Apr - 04 May 2011
European Society of Endocrinology