title: Detection of genomic amplification of the human telomerase gene TERC, a potential marker for triage of women with HPV-positive, abnormal Pap smears.
abstract: The vast majority of invasive cervical carcinomas harbor additional copies of the chromosome arm 3q, resulting in genomic amplification of the human telomerase gene TERC. Here, we evaluated TERC amplification in routinely collected liquid based cytology (LBC) samples with histologically confirmed diagnoses. A set of 78 LBC samples from a Swedish patient cohort were analyzed with a four-color fluorescence in situ hybridization probe panel that included TERC. Clinical follow-up included additional histological evaluation and Pap smears. Human papillomavirus status was available for all cases. The correlation of cytology, TERC amplification, human papillomavirus typing, and histological diagnosis showed that infection with high-risk human papillomavirus was detected in 64% of the LBC samples with normal histopathology, in 65% of the cervical intraepithelial neoplasia (CIN)1, 95% of the CIN2, 96% of the CIN3 lesions, and all carcinomas. Seven percent of the lesions with normal histopathology were positive for TERC amplification, 24% of the CIN1, 64% of the CIN2, 91% of the CIN3 lesions, and 100% of invasive carcinomas. This demonstrates that detection of genomic amplification of TERC in LBC samples can identify patients with histopathologically confirmed CIN3 or cancer. Indeed, the proportion of TERC-positive cases increases with the severity of dysplasia. Among the markers tested, detection of TERC amplification in cytological samples has the highest combined sensitivity and specificity for discernment of low-grade from high-grade dysplasia and cancer.
authors.affiliation: Department for Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital-Huddinge, Stockholm, Sweden.
authors.forename: Sonia
authors.initials: S
authors.lastname: Andersson
authors.forename: Pavani
authors.initials: P
authors.lastname: Sowjanya
authors.forename: Darawalee
authors.initials: D
authors.lastname: Wangsa
authors.forename: Anders
authors.initials: A
authors.lastname: Hjerpe
authors.forename: Bo
authors.initials: B
authors.lastname: Johansson
authors.forename: Gert
authors.initials: G
authors.lastname: Auer
authors.forename: Patti E
authors.initials: PE
authors.lastname: Gravitt
authors.forename: Catharina
authors.initials: C
authors.lastname: Larsson
authors.forename: Keng-Ling
authors.initials: KL
authors.lastname: Wallin
authors.forename: Thomas
authors.initials: T
authors.lastname: Ried
authors.forename: Kerstin
authors.initials: K
authors.lastname: Heselmeyer-Haddad
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D055088:Early Detection of Cancer; D005260:Female; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D065006:Papanicolaou Test; D027383:Papillomaviridae / Q000235:genetics / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000150:complications; D012372:ROC Curve; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology; D014626:Vaginal Smears; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D019098:Telomerase