title: Low somatostatin receptor subtype 2, but not dopamine receptor subtype 2 expression predicts the lack of biochemical response of somatotropinomas to treatment with somatostatin analogs.
abstract: OBJECTIVE
  To evaluate somatostatin receptor 2A (SSTR2A) and dopamine receptor 2 (DR2) protein expression in somatotropinomas and to relate it to response to somatostatin analogues (SA).
  
  
  METHODS
  SSTR2A and DR2 expression was analyzed by immunohistochemistry in 88 somatotropinomas from patients submitted to either pre-surgical or adjuvant SA treatment. Tumors were scored according to percentage of immunostained cells: 0 (< 25%), 1 (25-50%), and 2 (> 50%). Relation between protein expression and response to SA was performed in 66 patients. Response to SA was assessed by percent IGF-I reduction, being considered as an IGF-I per cent reduction higher than 50%. Disease control was also assessed (GH < 1.0 ng/ml and normal IGF-I).
  
  
  RESULTS
  SSTR2A and DR2 were expressed in 100% and 98% of tumors, respectively. Biochemical response and disease control rates were 48% and 32%, respectively. Median IGF-I percent reduction after 3 months of SA treatment was lower in the SSTR2A score 0 than in the scores 1 and 2 (p < 0.001, both), and after 6 months in the score 0 than in the score 1 (p = 0.001) and 2 (p < 0.001). Biochemical response and disease control were associated with SSTR2 expression (p < 0.001 and p = 0.004, respectively). A negative predictive value for biochemical response of 100% was found when a SSTR2A expression < 25%of immunostained cells cut-off point was considered. No relation was found between DR2 expression and biochemical response and disease control.
  
  
  CONCLUSIONS
  SSTR2A and DR2 are highly expressed in somatotropinomas. Low SSTR2A, but not DR2, expression is a negative predictive factor to response to SA.
authors.affiliation: Endocrinology Section, Hospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: L E A
authors.initials: LE
authors.lastname: Wildemberg
authors.forename: L V
authors.initials: LV
authors.lastname: Neto
authors.forename: D F
authors.initials: DF
authors.lastname: Costa
authors.forename: L E
authors.initials: LE
authors.lastname: Nasciuti
authors.forename: C M
authors.initials: CM
authors.lastname: Takiya
authors.forename: L M
authors.initials: LM
authors.lastname: Alves
authors.forename: A
authors.initials: A
authors.lastname: Rebora
authors.forename: F
authors.initials: F
authors.lastname: Minuto
authors.forename: D
authors.initials: D
authors.lastname: Ferone
authors.forename: M R
authors.initials: MR
authors.lastname: Gadelha
mesh_terms: D000172:Acromegaly / Q000188:drug therapy* / Q000378:metabolism; D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D016022:Case-Control Studies; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000188:drug therapy* / Q000378:metabolism; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use*; D011379:Prognosis; D011954:Receptors, Dopamine / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011954:Receptors, Dopamine; D017481:Receptors, Somatostatin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C093733:somatostatin receptor 2; D015282:Octreotide