title: Low aryl hydrocarbon receptor-interacting protein expression is a better marker of invasiveness in somatotropinomas than Ki-67 and p53.
abstract: BACKGROUND
  Some pituitary adenomas exhibit fast growth and invade surrounding structures. To date, there is no robust marker to predict invasiveness.
  
  
  OBJECTIVE
  To evaluate Ki-67, p53 and aryl hydrocarbon receptor-interacting protein (AIP) expression and compare these between invasive and noninvasive somatotropinomas and nonfunctioning pituitary adenomas (NFPAs).
  
  
  METHODS
  Protein expression was determined by immunohistochemistry. Tumors were classified according to percentage of immunolabeled nuclei for Ki-67 and p53. AIP immunopositivity was graded according to a score encompassing pattern and intensity. Invasiveness was defined according to radiological and surgical criteria.
  
  
  RESULTS
  Thirty-eight sporadic somatotropinomas were studied. Median Ki-67 labeling index in invasive and noninvasive tumors was 1.6 (range 0-20.6) and 0.26 (0-2.2), respectively (p = 0.01). With a 2.3% cut-off point obtained by ROC curve analysis, invasive adenomas were distinguished with 100% specificity, 39% sensitivity, and 63% accuracy. Low AIP expression was also correlated with tumor invasiveness (p = 0.001), with sensitivity, specificity and accuracy of 78, 80, and 79%, respectively. Expression of p53 was not different among tumors. Twenty-nine NFPAs were studied, with no significant difference between Ki-67, p53 and AIP expression in invasive and noninvasive tumors. High AIP expression was more frequent in NFPAs, with Ki-67 >3% (p = 0.051), especially when only gonadotrope cell adenomas (n = 25) were considered (p = 0.012).
  
  
  CONCLUSIONS
  These data suggest, for the first time, that AIP is a better marker of invasiveness in somatotropinomas than Ki-67 and p53. In addition, low AIP expression is observed in invasive somatotropinomas, in contrast with high AIP expression in NFPAs (mainly gonadotrope cell tumors) with high proliferative indices.
authors.affiliation: Serviço de Endocrinologia, Hospital Universitário Clementino Fraga Filho, Rio de Janeiro, Brazil.
authors.forename: Leandro
authors.initials: L
authors.lastname: Kasuki Jomori de Pinho
authors.forename: Leonardo
authors.initials: L
authors.lastname: Vieira Neto
authors.forename: Luiz Eduardo
authors.initials: LE
authors.lastname: Armondi Wildemberg
authors.forename: Emerson Leandro
authors.initials: EL
authors.lastname: Gasparetto
authors.forename: Jorge
authors.initials: J
authors.lastname: Marcondes
authors.forename: Bruno
authors.initials: B
authors.lastname: de Almeida Nunes
authors.forename: Christina M
authors.initials: CM
authors.lastname: Takiya
authors.forename: Mônica R
authors.initials: MR
authors.lastname: Gadelha
mesh_terms: D000236:Adenoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010911:Pituitary Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D012372:ROC Curve; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; C103265:aryl hydrocarbon receptor-interacting protein; D013006:Growth Hormone