title: Minichromosome maintenance protein 7 as prognostic marker of tumor aggressiveness in pituitary adenoma patients.
abstract: BACKGROUND
  Ki-67 labeling index (LI) is currently regarded as a useful prognostic marker of pituitary adenoma (PA) clinical behavior, although its relevance as a reliable clinical indicator is far from being universally accepted, since both validations and criticisms are found in the literature. Minichromosome maintenance 7 (MCM7), a cell-cycle regulator protein, has been recently proposed as a marker of tumor aggressiveness in tumors from many sites, including the CNS. Therefore, we evaluated MCM7, in comparison to Ki-67, as a potential marker of clinical outcome in PA.
  
  
  METHODS
  In this single-institution retrospective study, 97 patients with PA (23 ACTH, 12 GH, 29 PRL, 10 FSH/LH, and 23 non-secreting adenomas) were recruited and the prognostic value of both MCM7 and Ki-67 was evaluated by immunohistochemical techniques. In addition, p53 nuclear expression and mitotic index were also evaluated.
  
  
  RESULTS
  Twenty-six of the 97 PA patients recurred during the follow-up period. Cox's regression analysis showed that high nuclear expression of MCM7 LI, unlike Ki-67 LI, was directly associated with a higher (7.7-fold) risk of recurrence/progression. Kaplan-Meier analysis of recurrence/progression-free survival curves revealed that patients with high MCM7 LI (≥15%) had a shorter recurrence/progression-free survival than those with low MCM7 LI (<15%). Moreover, among patients with invasive tumors, high MCM7 LI identified those with the highest risk of recurrence/progression.
  
  
  CONCLUSIONS
  Data from this study suggest that MCM7 is a prognostic marker of clinical outcome in PA patients, more reliable and informative than Ki-67.
authors.affiliation: Department of Anatomic PathologyCatholic University, Largo F Vito 1, 00168 Rome, ItalyDepartment of Laboratory Medicine and PathobiologyUniversity of Toronto, Ontario, CanadaDepartments of EndocrinologyNeurosurgeryHistologyCatholic University, Rome, Italy antonella.coli@rm.unicatt.it.
authors.forename: Antonella
authors.initials: A
authors.lastname: Coli
authors.affiliation: Department of Anatomic PathologyCatholic University, Largo F Vito 1, 00168 Rome, ItalyDepartment of Laboratory Medicine and PathobiologyUniversity of Toronto, Ontario, CanadaDepartments of EndocrinologyNeurosurgeryHistologyCatholic University, Rome, Italy.
authors.forename: Sylvia L
authors.initials: SL
authors.lastname: Asa
authors.affiliation: Department of Anatomic PathologyCatholic University, Largo F Vito 1, 00168 Rome, ItalyDepartment of Laboratory Medicine and PathobiologyUniversity of Toronto, Ontario, CanadaDepartments of EndocrinologyNeurosurgeryHistologyCatholic University, Rome, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Fadda
authors.affiliation: Department of Anatomic PathologyCatholic University, Largo F Vito 1, 00168 Rome, ItalyDepartment of Laboratory Medicine and PathobiologyUniversity of Toronto, Ontario, CanadaDepartments of EndocrinologyNeurosurgeryHistologyCatholic University, Rome, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Scannone
authors.affiliation: Department of Anatomic PathologyCatholic University, Largo F Vito 1, 00168 Rome, ItalyDepartment of Laboratory Medicine and PathobiologyUniversity of Toronto, Ontario, CanadaDepartments of EndocrinologyNeurosurgeryHistologyCatholic University, Rome, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Chiloiro
authors.affiliation: Department of Anatomic PathologyCatholic University, Largo F Vito 1, 00168 Rome, ItalyDepartment of Laboratory Medicine and PathobiologyUniversity of Toronto, Ontario, CanadaDepartments of EndocrinologyNeurosurgeryHistologyCatholic University, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: De Marinis
authors.affiliation: Department of Anatomic PathologyCatholic University, Largo F Vito 1, 00168 Rome, ItalyDepartment of Laboratory Medicine and PathobiologyUniversity of Toronto, Ontario, CanadaDepartments of EndocrinologyNeurosurgeryHistologyCatholic University, Rome, Italy.
authors.forename: Liverana
authors.initials: L
authors.lastname: Lauretti
authors.affiliation: Department of Anatomic PathologyCatholic University, Largo F Vito 1, 00168 Rome, ItalyDepartment of Laboratory Medicine and PathobiologyUniversity of Toronto, Ontario, CanadaDepartments of EndocrinologyNeurosurgeryHistologyCatholic University, Rome, Italy.
authors.forename: Franco O
authors.initials: FO
authors.lastname: Ranelletti
authors.affiliation: Department of Anatomic PathologyCatholic University, Largo F Vito 1, 00168 Rome, ItalyDepartment of Laboratory Medicine and PathobiologyUniversity of Toronto, Ontario, CanadaDepartments of EndocrinologyNeurosurgeryHistologyCatholic University, Rome, Italy.
authors.forename: Libero
authors.initials: L
authors.lastname: Lauriola
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000378:metabolism / Q000473:pathology; D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D064168:Minichromosome Maintenance Complex Component 7 / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D015175:Prolactinoma / Q000378:metabolism / Q000473:pathology; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C101624:MCM7 protein, human; D064168:Minichromosome Maintenance Complex Component 7