title: The association of p16(INK4A) and fragile histidine triad gene expression and cervical lesions.
abstract: OBJECTIVE
  This cross-sectional study was intended to assess the association between immunohistochemical analysis of p16 and fragile histidine triad (FHIT) and the presence of precancerous cervical lesions.
  
  
  METHODS
  Women seen at Pérola Byington Hospital, São Paulo, Brazil, with histologically confirmed cervicitis (n = 31), cervical intraepithelial neoplasia (CIN) 1 (n = 30), CIN 2,3 (n = 30), and cervical cancer (n = 7) had also cervical material collected for liquid-based cytology, human papillomavirus Hybrid Capture 2 (HC2) test, and p16 and FHIT immunohistochemical reactions.
  
  
  RESULTS
  p16 and FHIT reactions were scored as the following: <1%, 1% to 5%, >5% to 25%, and >25%. Receiver operating curve analysis was used to select p16 and FHIT score cutoffs for further categorical analyses. All but one of the 37 CIN 2,3/cancer cases had a p16 score of greater than 1% to 5%. Among the 61 cervicitis/CIN 1 cases, 46 (75%) had a p16 score lower than 1% to 5%. In contrast, no association of FHIT expression and severity of cervical lesions could be demonstrated in this data set. Receiver operating curve analyses suggested the score of 1% to 5% for p16 as the cutoff that best discriminates CIN 2,3/cancer from cervicitis/CIN 1. No cutoff for FHIT scores could be suggested with data set.
  
  
  CONCLUSIONS
  p16, but not FHIT expression, has the potential to be used as complementary diagnostic tool to investigate human papillomavirus-induced cervical lesions, if these results are confirmed in larger studies.
authors.affiliation: Pathology Division of Adolfo Lutz Institute, São Paulo, Brazil. longatto@ecsaude.uminho.pt
authors.forename: Adhemar
authors.initials: A
authors.lastname: Longatto-Filho
authors.forename: Daniela
authors.initials: D
authors.lastname: Etlinger
authors.forename: Sônia Maria Miranda
authors.initials: SM
authors.lastname: Pereira
authors.forename: Cristina Takami
authors.initials: CT
authors.lastname: Kanamura
authors.forename: Celso
authors.initials: C
authors.lastname: di Loreto
authors.forename: Gilda da Cunha
authors.initials: Gda C
authors.lastname: Santos
authors.forename: Sérgio
authors.initials: S
authors.lastname: Makabe
authors.forename: José A
authors.initials: JA
authors.lastname: Marques
authors.forename: Carmen L F
authors.initials: CL
authors.lastname: Santoro
authors.forename: Gerson Botacini
authors.initials: GB
authors.lastname: das Dores
authors.forename: Adauto
authors.initials: A
authors.lastname: Castelo
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000378:metabolism*; D052685:Alphapapillomavirus; D019540:Area Under Curve; D003430:Cross-Sectional Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000378:metabolism; D012372:ROC Curve; D012680:Sensitivity and Specificity; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism*; D002575:Uterine Cervicitis / Q000235:genetics / Q000378:metabolism*; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase