title: Chromosomal gains measured in cytology samples from women with abnormal cervical cancer screening results.
abstract: OBJECTIVE
  Chromosomal gains at 3q26, 5p15 and 20q13 have been described in cervical precancer and cancer. We evaluated a novel fluorescence in situ hybridization (FISH) assay that detects gains at these three loci simultaneously as a possible biomarker for detecting cervical precancer.
  
  
  METHODS
  Chromosomal copy numbers at 3q26, 5p15, 20q13 and the centromere of chromosome7 (cen7) in liquid-based cytology specimens from 168 women enrolled in the Biopsy Study were determined by FISH. The number of cells with ≥ 3 or ≥ 4 signals for a genomic locus was enumerated and diagnostic test performance measures were calculated using receiver operating characteristic (ROC) analyses. Sensitivity and specificity values were determined for the detection of CIN2+ and/or HSIL.
  
  
  RESULTS
  The median number of cells with ≥ 3 signals increased with the severity of cervical lesion for each genomic locus (p-trend<0.02 for each locus). ROC analysis for the number of cells with ≥ 3 signals resulted in area under the curve values of 0.70 (95% CI: 0.54-0.86), 0.67 (0.52-0.83), 0.67 (0.51-0.83) and 0.78 (0.64-0.92) for 3q26, 5p15, 20q13 and cen7, respectively, for the detection of CIN2+ and/or HSIL. Positivity for gains at multiple loci resulted in only slightly better test performance measures than those for the individual probes for four distinct combinations of probes.
  
  
  CONCLUSIONS
  Chromosomal gains at 3q26, 5p15, 20q13 and cen7 are associated with severity of cervical lesions. Further studies are required to quantify risk stratification of FISH assays for cervical cancer screening.
authors.affiliation: Division of Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. luhnpa@mail.nih.gov
authors.forename: Patricia
authors.initials: P
authors.lastname: Luhn
authors.forename: Jane
authors.initials: J
authors.lastname: Houldsworth
authors.forename: Lynnette
authors.initials: L
authors.lastname: Cahill
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: Philip E
authors.initials: PE
authors.lastname: Castle
authors.forename: Rosemary E
authors.initials: RE
authors.lastname: Zuna
authors.forename: S Terence
authors.initials: ST
authors.lastname: Dunn
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gold
authors.forename: Joan
authors.initials: J
authors.lastname: Walker
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
mesh_terms: D000328:Adult; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000235:genetics*; D002890:Chromosomes, Human, Pair 20; D002893:Chromosomes, Human, Pair 3; D002895:Chromosomes, Human, Pair 5; D002897:Chromosomes, Human, Pair 7; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D011123:Polyploidy; D011230:Precancerous Conditions / Q000235:genetics*; D012372:ROC Curve; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor
keywords: 3q26; Cervical cancer; FISH; Genomic gains; HPV