Selective loss of somatostatin receptor 2 in octreotide-resistant growth hormone-secreting adenomas.
OBJECTIVE
The somatostatin analog octreotide preferentially binds to somatostatin receptor (sst) 2A and to a lesser extent to sst5. Although sst2A and sst5 mRNAs are consistently expressed in GH-secreting adenomas, octreotide controls GH secretion only in 65% of acromegalic patients. Hence, we investigated the immunocytochemical expression of sst in a large group of somatotroph tumors.


METHODS
Acromegalic patients, cared for in a university referral center, were either operated on without pretreatment (group A, n = 14) or pretreated with octreotide [median (minimum-maximum): dose 1250 (300-1500) mug/d for 5.6 (3-9) months] before surgery (group B, n = 20). In group B octreotide reduced GH secretion by more than 50% in 14 patients (70%) (GH responders). Six patients with less than 50% GH suppression were considered GH nonresponders. We used a panel of extensively characterized antibodies to determine the immunocytochemical sst status in somatotroph adenomas and compared their expression between the groups.


RESULTS
All group A tumors demonstrated immunoreactive sst2A, and all but one had sst5. A similar pattern was found in the GH responders of group B. In contrast, none of the GH nonresponders exhibited detectable sst2A (sst2A: GH responders vs. GH nonresponders, P < 0.0001), whereas sst5 was found in 70%. sst1 and sst3 were detected in 85 and 24% of all cases, independent of previous octreotide treatment.


CONCLUSIONS
Our findings suggest that octreotide resistance in GH-secreting adenomas occurs due to a selective loss of sst2A. The persistent expression of sst1 and sst5 receptors suggests that these tumors are potential targets for pan-somatostatin analogs.
Plöckinger
Ursula
U
Interdisziplinäres Stoffwechsel-Centrum, Endokrinologie, Diabetes, und Stoffwechsel, Med. Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, D-13353 Berlin, Germany.
Albrecht
Susann
S
Mawrin
Christian
C
Saeger
Wolfgang
W
Buchfelder
Michael
M
Petersenn
Stephan
S
Schulz
Stefan
S
D000236:Adenoma / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015282:Octreotide / Q000627:therapeutic use*; D017481:Receptors, Somatostatin / Q000032:analysis*
D018931:Antineoplastic Agents, Hormonal; D017481:Receptors, Somatostatin; D019382:Human Growth Hormone; C093733:somatostatin receptor 2; D015282:Octreotide