title: Expression of Ki-67, PTTG1, FGFR4, and SSTR 2, 3, and 5 in nonfunctioning pituitary adenomas: a high throughput TMA, immunohistochemical study.
abstract: BACKGROUND
  Nonfunctioning pituitary adenomas (NFPA) are the most common pituitary neoplasms. There is no clinical, biochemical, or histopathological marker that would accurately predict recurrence of NFPA.
  
  
  OBJECTIVE
  The aim of this study was to evaluate a large group of NFPA for the presence of potential markers of biological behavior.
  
  
  METHODS
  A cross-sectional study using a high throughput tissue microarray technology was conducted at tertiary care centers.
  
  
  METHODS
  Seventy-four gonadotroph and null cell adenomas were included in the tissue microarray. Using highly specific antibodies and appropriate controls, we determined the expression of Ki-67, pituitary tumor transforming gene 1, the N-terminally truncated pituitary tumor-derived fibroblast growth factor receptor-4 (FGFR4), as well as somatostatin receptor subtypes 2, 3, and 5 (SSTR2, -3, and -5), in an attempt to establish correlations and/or associations with clinical characteristics of the patients.
  
  
  RESULTS
  Median Ki-67 index was 1.49 (interquartile range, 0.62-2.49). Pituitary tumor transforming gene 1 nuclear immunoreactivity was found in all but one tumor (median percentage of positive nuclei, 11.44); immunopositivity for FGFR4 was found in the majority of the tumors, with variable levels of expression. The immunostaining score for SSTR2 was significantly higher than that for SSTR3 or SSTR5. FGFR4 expression correlated positively with SSTR2 and SSTR5 immunostaining scores (r = 0.59; P < 0.001; and r = 0.46; P < 0.001, respectively). Multivariate analysis revealed that the Ki-67 index was significantly associated with a tumor size greater than 3 cm (odds ratio, 2.32; 95% confidence interval, 1.17-4.58) as well as with tumor recurrence (odds ratio, 1.4; 95% confidence interval, 1.03-1.89).
  
  
  CONCLUSIONS
  Ki-67 is the most consistent marker of biological behavior in NFPA. The finding of significant amounts of SSTR2 and SSTR5 may have therapeutic implications regarding the use of somatostatin analogs in preventing tumor recurrence.
authors.affiliation: Endocrinology Service, Experimental Endocrinology Unit, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), 11560 México City, México.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ramírez
authors.forename: Sonia
authors.initials: S
authors.lastname: Cheng
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Vargas
authors.forename: Sylvia L
authors.initials: SL
authors.lastname: Asa
authors.forename: Shereen
authors.initials: S
authors.lastname: Ezzat
authors.forename: Baldomero
authors.initials: B
authors.lastname: González
authors.forename: Lourdes
authors.initials: L
authors.lastname: Cabrera
authors.forename: Gerardo
authors.initials: G
authors.lastname: Guinto
authors.forename: Moisés
authors.initials: M
authors.lastname: Mercado
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000378:metabolism*; D064249:Securin; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D017481:Receptors, Somatostatin; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; C103631:somatostatin receptor 3; C094573:somatostatin receptor 5; C093733:somatostatin receptor 2; C496371:FGFR4 protein, human; D051499:Receptor, Fibroblast Growth Factor, Type 4