title: 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.
abstract: 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.
authors.affiliation: 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.
authors.forename: Giselle F
authors.initials: GF
authors.lastname: Taboada
authors.forename: Raul M
authors.initials: RM
authors.lastname: Luque
authors.forename: Leonardo Vieira
authors.initials: LV
authors.lastname: Neto
authors.forename: Evelyn de O
authors.initials: Ede O
authors.lastname: Machado
authors.forename: Bruna C
authors.initials: BC
authors.lastname: Sbaffi
authors.forename: Romeu C
authors.initials: RC
authors.lastname: Domingues
authors.forename: Jorge B
authors.initials: JB
authors.lastname: Marcondes
authors.forename: Leila M C
authors.initials: LM
authors.lastname: Chimelli
authors.forename: Rosita
authors.initials: R
authors.lastname: Fontes
authors.forename: Paulo
authors.initials: P
authors.lastname: Niemeyer
authors.forename: Denise P
authors.initials: DP
authors.lastname: de Carvalho
authors.forename: Rhonda D
authors.initials: RD
authors.lastname: Kineman
authors.forename: Mônica R
authors.initials: MR
authors.lastname: Gadelha
mesh_terms: 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
chemical_list: 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