Quantitative analysis of somatostatin receptor subtypes (1-5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR.
OBJECTIVE
To determine whether the somatostatin receptor subtype (SSTR) expression profile correlates with hormonal and tumor volume responses to postsurgical octreotide long acting repeatable (OCT LAR) treatment.


METHODS
Quantitative real-time RT-PCR was used to evaluate the absolute mRNA copy numbers for all five SSTR subtypes in 22 somatotropinomas. Response to OCT LAR was studied by hormone levels (GH and IGF-I) and tumor volume (sella turcica magnetic resonance imaging).


RESULTS
SSTR5 was present at the highest level followed by SSTR2, SSTR3, SSTR1, and SSTR4 (2327 (1046-5555), 2098 (194-23 954), 97 (0-460), 14 (0-29 480), and 0 (0-652) copies respectively). Positive correlations were found between SSTR2 levels and the percentage decrease of GH and IGF-I after 3 (r=0.49, P<0.027 and r=0.49, P<0.029 respectively) and 6 (r=0.59, P<0.006 and r=0.58, P<0.008 respectively) months of OCT LAR. A negative correlation was found between SSTR5 mRNA levels and the percentage decrease of GH after 3 months of OCT LAR (r=-0.52, P=0.016, n=21). A higher SSTR2/SSTR5 ratio was observed among patients who obtained hormonal control with OCT LAR, when compared with those uncontrolled (2.4 (0.7-10) vs 0.3 (0.1-7.7), P=0.001). A ROC curve analysis showed a SSTR2/SSTR5 ratio of 1.3 as the best predictor of disease control, with a sensitivity of 88% and a specificity of 92% - area under curve, 0.9. A positive correlation was also found between SSTR2 mRNA levels and the percentage decrease in tumor volume after 6 months of OCT LAR (r=0.79, P=0.002, n=12).


CONCLUSIONS
Somatostatin receptor subtype 2 mRNA expression levels in somatotropinomas correlate positively with in vivo hormonal and tumor volume responses to OCT LAR.
Taboada
Giselle F
GF
Endocrinology Section, Radiology Section, Neurosurgery Section and Pathology Section, Hospital Universitário Clementino Fraga Filho, Instituto de Biofísica Carlos Chagas Filho, Federal University of Rio de Janeiro, 21941-913, Rio de Janeiro, Brazil.
Luque
Raul M
RM
Neto
Leonardo Vieira
LV
Machado
Evelyn de O
Ede O
Sbaffi
Bruna C
BC
Domingues
Romeu C
RC
Marcondes
Jorge B
JB
Chimelli
Leila M C
LM
Fontes
Rosita
R
Niemeyer
Paulo
P
de Carvalho
Denise P
DP
Kineman
Rhonda D
RD
Gadelha
Mônica R
MR
D000172:Acromegaly / Q000188:drug therapy / Q000503:physiopathology; D000236:Adenoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D005260:Female; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use*; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D008565:Membrane Proteins; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C103631:somatostatin receptor 3; C098681:somatostatin receptor subtype-4; C101130:somatostatin receptor type 1; C094573:somatostatin receptor 5; D013006:Growth Hormone; C093733:somatostatin receptor 2; D015282:Octreotide