Objective: To investigate the significance of genomic amplification of the telomerase RNA component (TERC) gene to serve as a genetic biomarker in the screening of cervical lesions.
Methods: A total of 715 cases were recruited, with liquid-based cytology diagnosis as normal (n = 347), atypical squamous cells of undetermined significance (ASCUS, n = 180), atypical squamous cells cannot exclude a high-grade lesion (ASC-H, n = 13), low-grade squamous intraepithelial lesions (LSIL, n = 115), high-grade squamous intraepithelial lesions (HSIL, n = 59) and atypical glandular cells (AGC, n = 1). The remaining cervical cells in the cytological preserving fluid were analyzed using a two-color fluorescence in situ hybridization (FISH) probe targeted to chromosome 3q26 containing TERC gene. The TERC gene findings were compared to the cytological and histological detected results, as well as high-risk human papillomavirus (HPV) detected results.
Results: Genomic amplification of TERC gene was found in 5.8% of normal specimens, 22.2% of ASCUS, 30.8% of ASC-H, 27.8% of LSIL, 86.4% of HSIL and 1/1 of AGC. The positive rate was significantly lower in normal, ASCUS, ASC-H and LSIL compared with HSIL (all P < 0.01). Significantly more cells with genomic amplification of TERC gene were found in cervical intraepithelial lesion (CIN) II-III than CINI (77.8% vs. 9.3%), as well as invasive cervical cancer (96.7% vs. 9.3%), both P < 0.01. The rate of TERC gene amplification was higher in HPV positive patients (33.5%) than in HPV negative patients (5.2%, P < 0.01). The sensitivity of TERC gene amplification was significantly higher than that of cytological screening (81.88% vs. 36.96%, P < 0.01) in the differentiation of CINII or higher and CINI or lower diseases, its specificity was higher than high-risk HPV test (93.32% vs. 33.93%, P < 0.01) and positive prediction value (81.29%) was similar with cytological method (86.44%, P > 0.05); but its negative prediction value (93.56%) was lower than HPV test (97.06%, P < 0.05).
Conclusions: The positive rates of TERC gene amplification increased as cervical diseases worsened. TERC gene amplification is related to HPV infection. The gain of chromosome 3q26 in cytological specimens is an effective molecular genetic biomarker in screening of CINII or higher and invasive cervical cancer.