Evaluation of genomic amplification of the human telomerase RNA component gene in the screening of cervical lesions

Abstract

To investigate the genomic amplification of the human telomerase RNA component (hTERC) gene in cervical cytology and evaluate its role in screening of cervical lesions. A total of 301 cases were recruited, with liquid-based cytology diagnoses as normal (n = 203), atypical squamous cells (ASC, n = 66), low-grade squamous intraepithelial lesions (LSIL, n = 18), and high-grade squamous intraepithelial lesions (HSIL, n = 14). Following cytological examination, the slides were analyzed using a two-color fluorescence in situ hybridization (FISH) probe targeted to chromosome 3q26 containing hTERC. The hTERC findings were compared to the cytologic and histologic results, as well as high-risk human papilloma viruses (HPV) results. Genomic amplification of hTERC was found in 3.0% (6/203) of normal specimens, 21.2% (14/66) of ASC, 44.4% (8/18) of LSIL and 92.9% (13/14) of HSIL, with a significant difference in each pair wise (all P < 0.05). Significantly more cells with 3q26 gain were found in cervical intraepithelial lesion (CIN)II than in CINI (75.0% vs. 20.0%), as well as in CINIII (86.7% vs. 20.0%) and squamous cervical cancer (SCC) than in CINI (100.0% vs. 20.0%)(all P < 0.01). The sensitivity of hTERC amplification was significantly higher than cytological screening (82.6% vs. 17.4%, P < 0.01), and its specificity was higher than high-risk HPV test (67.8% - 73.5% vs. 25.6% - 27.7%, P < 0.01) in the diagnosis of HSIL (CINII - III). The abnormal hTERC signal type mostly was 2:3 in CINI (84.9%); whereas in CINII - III, 2:3, 2:4 and 4:4 accounted for 44.6%, 24.8% and 17.8%, respectively. Testing the gain of chromosome 3q26 in cytological specimens using specific probe for hTERC is powerful in screening of HSIL, and the amplification patterns of 2:4 and 4:4 may serve as potential prognosis markers.