title: Ki-67 is a predictor of acromegaly control with octreotide LAR independent of SSTR2 status and relates to cytokeratin pattern.
abstract: BACKGROUND
  Only one study has evaluated Ki-67 as a predictor of the response to somatostatin analog therapy in acromegaly; however, other predictors like somatostatin receptor type 2 (SSTR2) and cytokeratin pattern expressions were not considered.
  
  
  OBJECTIVE
  To evaluate whether Ki-67 is a predictor of octreotide LAR (OCT-LAR) response in somatotropinomas independent of SSTR2 and cytokeratin expression patterns.
  
  
  METHODS
  Protein expression was analyzed by immunohistochemistry. The percentage of cell nuclei that were immunolabeled for Ki-67 and the percentage of cells with positive SSTR2 staining were calculated. SSTR2 expression was considered high when ≥25%, and a cutoff of 2.3% was designated for Ki-67. Tumors were classified as densely or sparsely granulated according to the cytokeratin pattern.
  
  
  RESULTS
  Thirty-one somatotropinomas were studied. Fourteen patients (45.2%) were controlled with OCT-LAR therapy. The median Ki-67 labeling index (LI) was higher in patients not controlled with OCT-LAR than in those controlled (1.63 and 0.15 respectively, P=0.002). Higher SSTR2 expression and densely granulated tumors were correlated with control as well (P=0.04 and 0.038 respectively). There was no difference in Ki-67 levels between patients with high and low SSTR2 expression (P=0.651). After multivariate analysis, both Ki-67 and SSTR2 remained statistically significant as predictors of OCT-LAR response (P=0.017 and 0.012 respectively). The Ki-67 LI was higher in sparsely than in densely granulated tumors (P=0.047).
  
  
  CONCLUSIONS
  Ki-67 is a predictor of response to OCT-LAR in acromegaly, independent of SSTR2 expression and relates to cytokeratin patterns.
authors.affiliation: Endocrinology Unit, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Leandro
authors.initials: L
authors.lastname: Kasuki
authors.forename: Luiz Eduardo Armondi
authors.initials: LE
authors.lastname: Wildemberg
authors.forename: Leonardo Vieira
authors.initials: LV
authors.lastname: Neto
authors.forename: Jorge
authors.initials: J
authors.lastname: Marcondes
authors.forename: Christina M
authors.initials: CM
authors.lastname: Takiya
authors.forename: Mônica R
authors.initials: MR
authors.lastname: Gadelha
mesh_terms: D000172:Acromegaly / Q000188:drug therapy / Q000378:metabolism*; D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism*; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D015282:Octreotide / Q000627:therapeutic use*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000378:metabolism; D055815:Young Adult
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019394:Ki-67 Antigen; D017481:Receptors, Somatostatin; D007633:Keratins; C093733:somatostatin receptor 2; D015282:Octreotide