title: Evaluation of MCM-2 expression in TMA cervical specimens.
abstract: BACKGROUND
  Minichromosome maintenance proteins (MCM) are highly expressed in actively replicating cells. The need for biological markers for cervical carcinoma and its precursor lesions is emerging. Our main aim was to determine the immunohistochemical expression of MCM-2 in HIV-positive and -negative dysplastic cervical specimens.
  
  
  METHODS
  Immunohistochemical analysis of MCM-2 was performed in a total of 352 cervical TMA specimens of normal control, low-grade CIN, high-grade CIN and invasive tumor. 38 specimens were from HIV-positive women. A receiver operating characteristic (ROC) curve was constructed to determine the best cutoff to diagnose high-grade CIN and invasive cervical cancer.
  
  
  RESULTS
  In the progression from normal epithelium to high-grade CIN and invasive tumor we found significant differences in the MCM-2 expression (p<0.05). Based on the ROC curve of 80% with an area under the curve (AUC) of 0.78, expression of MCM-2 to diagnose high-grade CIN and invasive tumor resulted in sensitivity of 81%, specificity of 66%, a positive predictive value (PPV) of 86% and a negative predictive value (NPV) of 57%. HIV-positive cervices revealed a decreasing expression of MCM-2 in both LGCIN and HGCIN compared with HIV-negative specimens (p<0.0001).
  
  
  CONCLUSIONS
  The present study suggests that immunohistochemical MCM-2 may not be a promising biomarker for diagnosing high-grade CIN and invasive cancer.
authors.affiliation: Laboratory Interdisciplinary of Medical Research, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil. nicol@ioc.fiocruz.br
authors.forename: Alcina F
authors.initials: AF
authors.lastname: Nicol
authors.forename: José R
authors.initials: JR
authors.lastname: Lapa e Silva
authors.forename: Cynthia B
authors.initials: CB
authors.lastname: Cunha
authors.forename: Sergio M
authors.initials: SM
authors.lastname: Amaro-Filho
authors.forename: Nathalia
authors.initials: N
authors.lastname: Oliveira
authors.forename: Beatriz
authors.initials: B
authors.lastname: Grinsztejn
authors.forename: Ruth Khalili
authors.initials: RK
authors.lastname: Friedman
authors.forename: Ruth
authors.initials: R
authors.lastname: Khalil
authors.forename: Fabio
authors.initials: F
authors.lastname: Russomano
authors.forename: Andrea
authors.initials: A
authors.lastname: Pires
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Golub
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Nuovo
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology / Q000821:virology; D060085:Coinfection; D004848:Epithelium / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005260:Female; D015870:Gene Expression; D006678:HIV / Q000502:physiology; D015658:HIV Infections / Q000378:metabolism / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D064111:Minichromosome Maintenance Complex Component 2; D060787:Neoplasm Grading; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D027383:Papillomaviridae / Q000502:physiology; D030361:Papillomavirus Infections / Q000378:metabolism / Q000821:virology; D011237:Predictive Value of Tests; D012372:ROC Curve; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2