title: Genomic amplification patterns of human telomerase RNA gene and C-MYC in liquid-based cytological specimens used for the detection of high-grade cervical intraepithelial neoplasia.
abstract: BACKGROUND
  The amplification of oncogenes initiated by high-risk human papillomavirus (HPV) infection is an early event in cervical carcinogenesis and can be used for cervical lesion diagnosis. We measured the genomic amplification rates and the patterns of human telomerase RNA gene (TERC) and C-MYC in the liquid-based cytological specimens to evaluate the diagnostic characteristics for the detection of high-grade cervical lesions.
  
  
  METHODS
  Two hundred and forty-three residual cytological specimens were obtained from outpatients aged 25 to 64 years at Qilu Hospital, Shandong University. The specimens were evaluated by fluorescence in situ hybridization (FISH) using chromosome probes to TERC (3q26) and C-MYC (8q24). All of the patients underwent colposcopic examination and histological evaluation. A Chi-square test was used for categorical data analysis.
  
  
  RESULTS
  In the normal, cervical intraepithelial neoplasia grade 1 (CIN1), grade 2 (CIN2), grade 3 (CIN3) and squamous cervical cancer (SCC) cases, the TERC positive rates were 9.2%, 17.2%, 76.2%, 100.0% and 100.0%, respectively; the C-MYC positive rates were 20.7%, 31.0%, 71.4%, 81.8% and 100.0%, respectively. The TERC and C-MYC positive rates were higher in the CIN2+ (CIN2, CIN3 and SCC) cases than in the normal and CIN1 cases (p < 0.01). Compared with cytological analysis, the TERC test showed higher sensitivity (90.0% vs. 84.0%) and higher specificity (89.6% vs. 64.3%). The C-MYC test showed lower sensitivity (80.0% vs. 84.0%) and higher specificity (77.7% vs. 64.3%). Using a cut-off value of 5% or more aberrant cells, the TERC test showed the highest combination of sensitivity and specificity. The CIN2+ group showed more high-level TERC gene copy number (GCN) cells than did the normal/CIN1 group (p < 0.05). For C-MYC, no significant difference between the two histological categories was detected (p > 0.05).
  
  
  CONCLUSIONS
  The TERC test is highly sensitive and is therefore suitable for cervical cancer screening. The C-MYC test is not suitable for cancer screening because of its lower sensitivity. The amplification patterns of TERC become more diverse and complex as the severity of cervical diseases increases, whereas for C-MYC, the amplification patterns are similar between the normal/CIN1 and CIN2+ groups.
  The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1308004512669913.
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, People's Republic of China.
authors.forename: Shaomin
authors.initials: S
authors.lastname: Chen
authors.forename: Ziyan
authors.initials: Z
authors.lastname: Yang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Qiao
authors.forename: Baoxia
authors.initials: B
authors.lastname: Cui
authors.forename: Youzhong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Beihua
authors.initials: B
authors.lastname: Kong
mesh_terms: D000328:Adult; D003584:Cytological Techniques; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D011379:Prognosis; D012313:RNA / Q000235:genetics*; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D019098:Telomerase / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase