title: Pituitary tumor transforming gene and insulin-like growth factor 1 receptor expression and immunohistochemical measurement of Ki-67 as potential prognostic markers of pituitary tumors aggressiveness.
abstract: OBJECTIVE
  The ability to predict recurrence of pituitary adenoma (PA) after surgery may be helpful to determine follow-up frequency and the need for adjuvant treatment. The purpose of this study was to assess the prognostic capacity of pituitary tumor transforming gene (PTTG), insulin-like growth factor 1 receptor (IGF1R), and Ki-67.
  
  
  METHODS
  In this retrospective study, the normalized copy number (NCN) of PTIG and IGF1R mRNA was measured using RT-PCR, and the Ki-67 index was measured by immunohistochemistry in 46 PA samples. Clinical data, histological subtype, and radiographic characteristics were collected to assess associations between variables and tumor behavior. Progression of tumor remnants and its association to markers was also studied in 14 patients with no adjuvant treatment after surgery followed up for 46±36 months.
  
  
  RESULTS
  Extrasellar tumors had a lower PTTG expression as compared to sellar tumors (0.065 [1st-3rd quartile: 0.000-0.089] NCN vs. 0.135 [0.105-0.159] NCN, p=0.04). IGF1R expression changed depending on histological subtype (p=0.014), and was greater in tumor with remnant growth greater than 20% during follow-up (10.69±3.84 NCN vs. 5.44±3.55 NCN, p=0.014).
  
  
  CONCLUSIONS
  Our results suggest that the IGF1R is a more helpful molecular marker than PTTG in PA management. Ki-67 showed no association to tumor behavior. However, the potential of these markers should be established in future studies with standardized methods and on larger samples.
authors: Endocrinology Department, Research Unit, Hospital General Universitario Alicante, Alicante, Spain.
authors: Laura
authors: L
authors: Sánchez-Tejada
authors: Ruth
authors: R
authors: Sánchez-Ortiga
authors: Oscar
authors: O
authors: Moreno-Pérez
authors: Carmen Fajardo
authors: CF
authors: Montañana
authors: Maria
authors: M
authors: Niveiro
authors: Nicholas A
authors: NA
authors: Tritos
authors: Antonio M Picó
authors: AM
authors: Alfonso
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D018491:Dopamine Agonists / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007016:Hypophysectomy; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D010911:Pituitary Neoplasms / Q000737:chemistry* / Q000145:classification / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000032:analysis / Q000096:biosynthesis; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D012189:Retrospective Studies; D064249:Securin / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D013004:Somatostatin / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D018491:Dopamine Agonists; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; D013004:Somatostatin; D017526:Receptor, IGF Type 1
keywords: ACTH; Adenoma hipofisario; Antígeno Ki-67; CT; DA; FFPE; FPA; GH; GT; Humanos; Humans; IGF1R; Insulin-like growth factor 1 receptor; Ki-67 antigen; LT; MAPK; MRI; NC; NFPA; PA; PI3K/Akt; PRL; PTTG; Pituitary adenoma; Pituitary tumor transforming gene protein; Proteína del gen transformador de tumores hipofisarios; ROC; RT-PCR; Receptor del factor de crecimiento insulinoide 1; SSa; ST; TSH; TT; Thyroid stimulating hormone; Thyrotrophic adenomas; adrenocorticotropic hormone; corticotrophic adenomas; dopamine agonist; formalin-fixes and paraffin-embedded; functioning pituitary adenoma; gonadotrophic adenomas; growth hormone; insulin-like growth factor 1 receptor; lactotrophic adenomas; magnetic resonance imaging; mitogen-activated protein kinases; non-functioning pituitary adenoma; null-cell adenomas; phosphoinositide 3-kinase/Akt pathway; pituitary adenomas; pituitary tumor transforming gene; prolactin; real time polymerase chain reaction; receiver operating characteristics; somatostatin analogs; somatotrophic adenomas