title: Prediction of outcome in patients with low-grade squamous intraepithelial lesions by fluorescence in situ hybridization analysis of human papillomavirus, TERC, and MYC.
abstract: BACKGROUND
  Cytology is an excellent method with which to diagnose preinvasive lesions of the uterine cervix, but it suffers from limited specificity for clinically significant lesions. Supplementary methods might predict the natural course of the detected lesions. The objective of the current study was to test whether a multicolor fluorescence in situ hybridization (FISH) assay might help to stratify abnormal results of Papanicolaou tests.
  
  
  METHODS
  A total of 219 liquid-based cytology specimens of low-grade squamous intraepithelial lesions (LSIL), 49 atypical squamous cells of undetermined significance (ASCUS) specimens, 52 high-grade squamous intraepithelial lesion (HSIL) specimens, and 50 normal samples were assessed by FISH with probes for the human papillomavirus (HPV), MYC, and telomerase RNA component (TERC). Subtyping of HPV by polymerase chain reaction (PCR) was performed in a subset of cases (n=206).
  
  
  RESULTS
  There was a significant correlation found between HPV detection by FISH and PCR (P<.0001). In patients with LSILs, the presence of HPV detected by FISH was significantly associated with disease progression (P<.0001). An increased MYC and/or TERC gene copy number (>2 signals in>10% of cells) prevailed in 43% of ASCUS specimens and was more frequent in HSIL (85%) than in LSIL (33%) (HSIL vs LSIL: P<.0001). Increased TERC gene copy number was significantly correlated with progression of LSIL (P<.01; odds ratio, 7.44; area under the receiver operating characteristic curve, 0.73; positive predictive value, 0.30; negative predictive value, 0.94) CONCLUSIONS: The detection of HPV by FISH analysis is feasible in liquid-based cytology and is significantly correlated with HPV analysis by PCR. The analysis of TERC gene copy number may be useful for risk stratification in patients with LSIL.
authors: Institute of Pathology, University Hospital Basel, Basel, Switzerland. Ellen.Obermann@usb.ch
authors: Ellen C
authors: EC
authors: Obermann
authors: Spasenija
authors: S
authors: Savic Prince
authors: Audrey
authors: A
authors: Barascud
authors: Bruno
authors: B
authors: Grilli
authors: Michelle
authors: M
authors: Herzog
authors: Daniela
authors: D
authors: Kaup
authors: Gieri
authors: G
authors: Cathomas
authors: Brigitte
authors: B
authors: Frey Tirri
authors: Inti
authors: I
authors: Zlobec
authors: Edward
authors: E
authors: Wight
authors: Lukas
authors: L
authors: Bubendorf
mesh_terms: D019540:Area Under Curve; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000821:virology; D005260:Female; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis / Q000821:virology; D016133:Polymerase Chain Reaction; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis* / Q000235:genetics; D012313:RNA / Q000032:analysis* / Q000235:genetics; D012372:ROC Curve; D019098:Telomerase / Q000032:analysis* / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000235:genetics / Q000821:virology
chemical_list: D016271:Proto-Oncogene Proteins c-myc; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase
keywords: MYC; cervical cytology; fluorescence in situ hybridization; human papillomavirus; squamous intraepithelial lesion; telomerase RNA component (TERC)