Human telomerase RNA component (hTERC) gene expression and chromosome 7 ploidy correlate positively with histological grade of cervical intraepithelial neoplasia.

Abstract

Cervical cancer screening by primary human papilloma virus detection and cytology is fraught with low specificity and variable sensitivity, respectively. Cytology-histology correlation remains modest. Biomarkers associated with early genetic events in cervical squamous carcinogenesis and detectable in cytology material are likely to be relevant. Human telomerase RNA component (hTERC) gene overexpression and aneuploidy are promising candidates in view of their reported early and consistent association with cervical squamous oncogenesis. We analysed hTERC gene expression and chromosome 7 ploidy by fluorescent in-situ hybridisation (FISH) in 50 women with cytological precursor squamous intraepithelial lesions and available histology outcomes. Results were expressed as percentages of cells showing ≥3 signals, mean signals/nucleus, and maximum amplitude across various cytology and histology categories. Proportions of positive cases were calculated from threshold values derived from 6 controls. Distribution of above indices with respect to ≥cervical intraepithelial neoplasia 2 (CIN2) was explored. For both genetic aberrations, there was significant positive correlation (for all indices) between the proportion of positive cases and worsening cytological and histological outcomes (P<.05), with significant intergroup differences (P<.05). High-grade lesions (≥CIN2) had significantly higher results compared to <CIN2 lesions (P≤.001). In five discordant cases with ≥CIN2 under- or overdiagnosed on cytology, FISH supported the histological diagnosis. HTERC gene amplification and chromosome 7 ploidy showed positive association with cervical squamous carcinogenesis and could be relevant in settings of discrepant cytology-histology correlation.