PMID- 23408758 OWN - NLM STAT- MEDLINE DCOM- 20131021 LR - 20221207 IS - 1934-6638 (Electronic) IS - 1934-662X (Linking) VI - 121 IP - 8 DP - 2013 Aug TI - Prediction of outcome in patients with low-grade squamous intraepithelial lesions by fluorescence in situ hybridization analysis of human papillomavirus, TERC, and MYC. PG - 423-31 LID - 10.1002/cncy.21280 [doi] AB - 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. CI - Copyright (c) 2013 American Cancer Society. FAU - Obermann, Ellen C AU - Obermann EC AD - Institute of Pathology, University Hospital Basel, Basel, Switzerland. Ellen.Obermann@usb.ch FAU - Savic Prince, Spasenija AU - Savic Prince S FAU - Barascud, Audrey AU - Barascud A FAU - Grilli, Bruno AU - Grilli B FAU - Herzog, Michelle AU - Herzog M FAU - Kaup, Daniela AU - Kaup D FAU - Cathomas, Gieri AU - Cathomas G FAU - Frey Tirri, Brigitte AU - Frey Tirri B FAU - Zlobec, Inti AU - Zlobec I FAU - Wight, Edward AU - Wight E FAU - Bubendorf, Lukas AU - Bubendorf L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130213 PL - United States TA - Cancer Cytopathol JT - Cancer cytopathology JID - 101499453 RN - 0 (Proto-Oncogene Proteins c-myc) RN - 0 (telomerase RNA) RN - 63231-63-0 (RNA) RN - EC 2.7.7.49 (Telomerase) SB - IM MH - Area Under Curve MH - Carcinoma, Squamous Cell/*diagnosis/virology MH - Female MH - Gene Dosage MH - Humans MH - In Situ Hybridization, Fluorescence/*methods MH - Papillomaviridae MH - Papillomavirus Infections/complications/diagnosis/virology MH - Polymerase Chain Reaction MH - Proto-Oncogene Proteins c-myc/*analysis/genetics MH - RNA/*analysis/genetics MH - ROC Curve MH - Telomerase/*analysis/genetics MH - Uterine Cervical Neoplasms/*diagnosis/genetics/virology MH - Uterine Cervical Dysplasia/*diagnosis/genetics/virology OTO - NOTNLM OT - MYC OT - cervical cytology OT - fluorescence in situ hybridization OT - human papillomavirus OT - squamous intraepithelial lesion OT - telomerase RNA component (TERC) EDAT- 2013/02/15 06:00 MHDA- 2013/10/22 06:00 CRDT- 2013/02/15 06:00 PHST- 2012/12/10 00:00 [received] PHST- 2012/12/27 00:00 [revised] PHST- 2013/01/02 00:00 [accepted] PHST- 2013/02/15 06:00 [entrez] PHST- 2013/02/15 06:00 [pubmed] PHST- 2013/10/22 06:00 [medline] AID - 10.1002/cncy.21280 [doi] PST - ppublish SO - Cancer Cytopathol. 2013 Aug;121(8):423-31. doi: 10.1002/cncy.21280. Epub 2013 Feb 13.