The clinical response to somatostatin analogues in acromegaly correlates to the somatostatin receptor subtype 2a protein expression of the adenoma.
OBJECTIVE
Reduced expression of the somatostatin receptor subtype 2 (SSTR2) has been suggested as an explanation for the poor response to octreotide in acromegaly, but studies correlating levels of SSTR2 mRNA to octreotide efficacy have been contradictory. Some studies have found better responses to somatostatin analogues in G-protein alpha subunit (Gsalpha) mutation (gsp oncogene)-positive adenomas. The aim of this study was to determine adenoma SSTR2a protein expression and gsp status in a large group of patients with acromegaly, and relate this to the clinical effect of octreotide.


METHODS
Seventy-one patients were included. All underwent transsphenoidal surgery, 23 patients after preoperative octreotide treatment.


METHODS
The adenoma SSTR2a expression was examined by immunohistochemistry and Western blot analysis, and gsp status determined. An acute octreotide test was performed, and the change in IGF-1 level after 6 months preoperative octreotide treatment was recorded.


RESULTS
The acute octreotide response in non-pretreated patients and the preoperative long-term octreotide response were significantly better in patients with adenomas containing a large proportion of cells that stained positively for SSTR2a by immunohistochemistry. However, the SSTR2a protein level assessed by Western blot did not correlate with the octreotide response. The preoperatively treated group had lower SSTR2a protein levels and fewer adenomas with a large percentage of positively stained cells. The gsp oncogene was detected in 43% of the adenomas but did not correlate to the octreotide response.


CONCLUSIONS
The clinical effect of octreotide correlates with the proportion of cells positive for SSTR2a in immunohistochemical staining, rather than the adenoma SSTR2a protein level. There may be a down-regulation of SSTR2a during octreotide treatment.
Fougner
Stine L
SL
Research Institute for Internal Medicine, University of Oslo, Oslo, Norway. s.l.fougner@medisin.uio.no
Borota
Olivera Casar
OC
Berg
Jens Petter
JP
Hald
John K
JK
Ramm-Pettersen
Jon
J
Bollerslev
Jens
J
D000172:Acromegaly / Q000188:drug therapy* / Q000235:genetics; D000236:Adenoma / Q000188:drug therapy* / Q000235:genetics; D000328:Adult; D005260:Female; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use*; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D044385:GTP-Binding Protein alpha Subunits; D017481:Receptors, Somatostatin; D013004:Somatostatin; C093733:somatostatin receptor 2; D015282:Octreotide