Is somatostatin receptor expression in adenomas related to pharmacological response?
The clinical response to somatostatin analogue (SMS) treatment in acromegaly is highly variable. In unselected, previously untreated patients, biochemical control is achieved in 2050% of patients, and mean overall tumour shrinkage has been reported to 2540%.
The somatostatin analogues exert their effects through binding to the somatostatin receptor (SSTR) localized in the cell membrane. The available analogues bind with high affinity to SSTR2, less to SSTR5 and lower to SSTR3. It can therefore be expected that the adenoma expression of SSTR2 is important for the SMS response. Indeed, the first studies of SSTR2 mRNA from adenoma extracts demonstrated a correlation to in vivo octreotide response either in an acute test or long-term treatment. This has later been confirmed in studies of SSTR2a protein expression and long-term SMS treatment. Two studies of 18/20 patients have shown that the percentage GH or IGF1 reduction during treatment is larger in adenomas with a high proportion of SSTR2a positive cells in adenoma immunohistochemistry. Another study found that patients with <50% GH reduction during preoperative treatment did not express SSTR2a in immunohistochemistry, in contrast to octreotide responders. However, the studies also demonstrated patients with low SSTR2a positivity and good octreotide response, and patients with high SSTR2a positivity and very poor octreotide efficacy. This suggests that not only adenoma SSTR2 expression determines the clinical efficacy of SMS. One could expect an impact of SSTR5, but the research of SSTR5 expression and SMS response has not been conclusive. However, the densely granulated somaototroph adenomas respond significantly better to SMS treatment compared to sparsely granulated adenomas, but they also display lower SSTR2a protein expression. Despite a lower SSTR2a protein expression in gsp positive adenomas, they do not respond better to long-term SMS treatment. This can imply additional mechanisms important for SMS response in these adenomas.
Declaration of interest: The author declares that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.