Detection of TERC Amplification in Cervical Epithelial Cells for the Diagnosis of High-Grade Cervical Lesions and Invasive Cancer

Abstract

Because the activation of telomerase is a relatively early event in the progression of cervical carcinogenesis , the expression of the human telomerase RNA gene , TERC, has the potential to serve as a biomarker for both the diagnosis and prognosis of cervical neoplasias. In total , 83 research centers participated in the study , and 7786 patients were enrolled. TERC amplification was detected using a dual-color fluorescence in situ hybridization (FISH) probe set, and these results were compared with cytological and histological results , testing for high-risk human papillomavirus (HPV) DNA (n ‫؍‬ 2316 for the HPV DNA test), as well as patient age. TERC amplification was found to be increased in more advanced cases of cervical carcinogenesis. Moreover , a Youden's index value and the area under the receiver operating characteristic (ROC) curve were also calculated for samples with TERC amplification and found to be higher than the same values calculated for both cytology and highrisk HPV analyses of the same samples. With regard to cytological ASCUS and LSIL findings , the combination of HPV ؉ TERC testing showed the potential to provide effective triaging to detect CIN2 ؉ . Therefore, TERC amplification represents a valuable genetic biomarker , which in combination with an evaluation of cytology or HPV testing , can achieve higher sensitivity and specificity in distinguishing high-grade cervi- Cervical cancer is the second most common cancer in women, and in 2005, more than 250,000 deaths worldwide were the result of cervical cancer.1 Because ϳ80% of all cervical cancer cases are diagnosed in developing countries, in China, there are ϳ135,000 new cases and 50,000 deaths each year due to this disease.2 Without improvements in the treatments available, the number of cases of cervical cancer are projected to rise by almost 25% over the next 10 years. Therefore, to decrease the incidence and mortality associated with cervical cancer, effective approaches are needed to facilitate the screening and diagnosis of cervical precancerous lesions, especially high-grade lesions.The use of cervical cytopathologic examinations has reduced the incidence of cervical cancer in many countries, 3,4 however the low sensitivity and high variability of this method has limited its significance. 5 With human papillomavirus (HPV) being the main cause of cervical cancer, detection of HPV DNA has become an important supplement to cytologic evaluations performed during cervical cancer screenings.6,7 However, most women who are infected with HPV eliminate the virus and do not progress to high-grade disorders, thereby decreasing the specificity of HPV DNA tests for the detection of cervical cancer. 8 The infection and integration of HPV into epithelial cells are key steps in the induction of malignant alterations in cervical cancer; however, there are additional genomic events that also occur.9 One of the events associated with cervical cancer is an increase in copy number of the long arm of chromosome 3 (3q).

Whole transcriptome analysis reveals dysregulated oncogenic lncRNAs in natural killer/T-cell lymphoma and establishes MIR155HG as a target of PRDM1

“…TERC overexpression is associated with many cancer types, including lung cancer 66 and cervical neoplasia. 67 However, TERC did not show upregulation in NKTCL, suggesting that it may not have a notable role in pathobiology of this neoplasm. Biological functions of most lncRNAs transcriptionally regulated by PRDM1 are currently unknown, and further studies involving in vitro functional characterization may be needed.…”

Molecular cytogenetic analyses of hTERC (3q26) and MYC (8q24) genes amplifications in correlation with oncogenic human papillomavirus infection in Czech patients with cervical intraepithelial neoplasia and cervical carcinomas

“…Jiang et al [19] observed hTERC amplification in 94.9% of patients with squamous cell carcinoma, Yin el al. [22] detected this alteration even in 100% of women with invasive carcinoma of cervix uteri.…”

“…However, simultaneous amplification of hTERC and MYC detected in 25% (3) of women without pathology indicates that patients with high risk can also be in this group. Jiang et al and Chen et al [19,20] analyzed hTERC gene in 178 and 164 patients without oncological finding and the amplification of this gene was found in 6.2% and 9.2% respectively. Our observed results can be caused by small number of tested women.…”

“…Another two Chinese studies also confirmed that increase of hTERC amplification was correlated with higher histological grade of premalignant lesions. In large study, Jiang et al [19] examined specimens of 4851 women with premalignant lesions, positivity of hTERC gain was detected in 20.8% of women with CIN I, in 68.6% patients with CIN II and in 82.4% women with CIN III. Similarly, in study of Jin et al [9] amplification of hTERC occurred in 18.2% (6/33) of CIN I patients, in 66.7% (6/9) of CIN II patients and in 84.6% (22/26) of CIN III patients.…”

253: Expression of TRF2 and its prognostic relevance in advanced stage cervical cancer patients

“…The clinical potential of telomeric proteins in the treatment of cancer was subject of research by several studies [15][16][17][18]. The altered expression of telomere capping factors, such as TRF2, could enhance telomeric damage, cause to an instability at chromosomal ends, telomerase dependent shortening of telomeres and undesirable activation of DNA repair mechanisms.…”