Correlation of in vitro and in vivo somatotropic adenoma responsiveness to somatostatin analogs and dopamine agonists with immunohistochemical evaluation of somatostatin and dopamine receptors and electron microscopy.
OBJECTIVE
Twenty-four pituitary adenomas from acromegalic patients (13 females, 11 males; age range 19-65 yr) were characterized for somatostatin receptor subtype 2A (sst(2A)), dopamine D(2) receptor (D(2)R), GH, and prolactin (PRL) expression by immunohistochemistry, and results correlated with the in vitro and in vivo hormone responses to octreotide and quinagolide. In nine cases, GH and PRL content was further studied by immunoelectron microscopy.


RESULTS
Immunoreactivity was semiquantitatively scored as 2 (>50% stained cells), 1 (10-50% stained cells), and 0 (<10% stained cells). Sst(2A) was scored as 2 in 13 cases, 1 in 10, and 0 in one; D(2)R was scored as 2 in 13 cases, 1 in nine, and 0 in 2; GH was 2 in 15 cases and 1 in nine; PRL was 2 in six cases, 1 in 13, and 0 in 5. Sst(2A) was positively correlated with in vitro (P = 0.003) and in vivo (P = 0.006) percent GH suppression by octreotide and with the chronic suppression of IGF-I by somatostatin analogs (P =0.008). D(2)R was positively correlated with in vitro percent GH (P =0.000) and PRL (P =0.005) suppression by quinagolide. Electron microscopy revealed two pure somatotroph adenomas, five somatomammotrophs with a variable coexpression of GH and PRL in the same cells, and two tumors consisting of mixed cell types, which were less sensitive to quinagolide and octreotide.


CONCLUSIONS
Sst(2A) and D(2)R are frequently coexpressed in adenomas from acromegalic patients, and immunohistochemistry may be helpful in characterizing receptor expression in pituitary adenomas to select patients responsive to different treatments.
Ferone
Diego
D
Department of Internal Medicine, Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands. ferone@unige.it
de Herder
Wouter W
WW
Pivonello
Rosario
R
Kros
Johan M
JM
van Koetsveld
Peter M
PM
de Jong
Ton
T
Minuto
Francesco
F
Colao
Annamaria
A
Lamberts
Steven W J
SW
Hofland
Leo J
LJ
D000236:Adenoma / Q000737:chemistry / Q000188:drug therapy* / Q000648:ultrastructure; D000328:Adult; D000634:Aminoquinolines / Q000627:therapeutic use*; D018491:Dopamine Agonists / Q000627:therapeutic use*; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000737:chemistry / Q000188:drug therapy* / Q000648:ultrastructure; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use*; D011388:Prolactin / Q000097:blood; D017448:Receptors, Dopamine D2 / Q000032:analysis*; D017481:Receptors, Somatostatin / Q000032:analysis*
D000634:Aminoquinolines; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D017481:Receptors, Somatostatin; C106140:somatostatin receptor sst2A; D019382:Human Growth Hormone; C046650:quinagolide; D011388:Prolactin; D015282:Octreotide