Amplification of the chromosome 3q26 region shows high negative predictive value for nonmalignant transformation of LSIL cytologic finding

Jalali, G. Reza; Herzog, Thomas J.; Dziura, Bruce; Walat, Robert J.; Kilpatrick, Michael W.

doi:10.1016/j.ajog.2009.12.016

Cited by 25 publications

(18 citation statements)

References 23 publications

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“…These findings, comparable with previous studies, strongly support the potential clinical usefulness of this genetic test for the correct management of women with borderline/low-grade cervical abnormalities [36,37,38,39,40]. …”

Section: Discussionsupporting

confidence: 90%

Clinical Role of the Detection of Human Telomerase RNA Component Gene Amplification by Fluorescence in situ Hybridization on Liquid-Based Cervical Samples: Comparison with Human Papillomavirus-DNA Testing and Histopathology

Zappacosta

Ianieri²,

Buca³

et al. 2015

Acta Cytologica

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Objective: This study was designed to evaluate whether the adjunct of human telomerase RNA component (hTERC) fluorescence in situ hybridization (FISH) analysis to cytological diagnosis and human papillomavirus (HPV)-DNA testing may serve as a predictive marker for distinguishing cervical lesions destined to regress from those at high risk of progression towards invasive cancer. Study Design: hTERC FISH analysis was performed on 54 residual liquid-based cytology specimens obtained from women referred to colposcopy for the detection of atypical squamous cells of undetermined significance or worse (ASCUS+) lesions. Histological diagnosis was considered the gold standard and cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) as the worst outcome. Results: Oncogenic HPV-DNA was found in 96.3% of the specimens. Among these, 38.5% revealed a CIN2+ diagnosis. hTERC gene amplification was detected in 37% of the cases; among these, 70% showed up as CIN2+. hTERC FISH analysis significantly improves the specificity and positive predictive value of HPV-DNA testing, thus differentiating patients with a CIN2+ diagnosis from those with a CIN2- diagnosis. Conclusions: Despite the limitation of a small study sample, our findings provide promising data, indicating the possible role of hTERC analysis in the assessment of the risk of developing cervical cancer. This approach would implement the specificity of DNA testing, avoiding overtreatment at the same time. Prospective follow-up studies are needed with the aim of introducing hTERC FISH into decision-making algorithms.

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Section: Discussionsupporting

confidence: 90%

Clinical Role of the Detection of Human Telomerase RNA Component Gene Amplification by Fluorescence in situ Hybridization on Liquid-Based Cervical Samples: Comparison with Human Papillomavirus-DNA Testing and Histopathology

Zappacosta

Ianieri²,

Buca³

et al. 2015

Acta Cytologica

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“…27 In this study, the combination of detecting TERC amplification and testing for high-risk HPV DNA helped to triage ASCUS and LSIL cytologic findings. For example, the sensitivity of detecting CIN2 ϩ using HPV ϩ TERC testing was 96.4% in the ASCUS cytologic group and 99.1% in the LSIL group, with NPV values of 96.5% and 97.5%, respectively.…”

Section: Discussionmentioning

confidence: 94%

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

Jiang

Wei

et al. 2010

The Journal of Molecular Diagnostics

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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).

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“…A 3q26 gain has been reported to increase in frequency from normal cervical epithelium, to CIN, and then to invasive carcinoma [24,25]. Recent studies have examined the use of 3q26 gain measurements as a predictor of regression or progression of cervical LSIL [26][27][28]. Prospective studies in larger numbers of women with LSIL are ongoing to establish more reliable sensitivity, specificity, PPV and NPV data.…”

Section: Discussionmentioning

confidence: 99%

Methylated ZNF582 gene as a marker for triage of women with Pap smear reporting low-grade squamous intraepithelial lesions — A Taiwanese Gynecologic Oncology Group (TGOG) study

Lin

Chen

Chang

et al. 2014

Gynecologic Oncology

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Amplification of the chromosome 3q26 region shows high negative predictive value for nonmalignant transformation of LSIL cytologic finding

Cited by 25 publications

References 23 publications

Clinical Role of the Detection of Human Telomerase RNA Component Gene Amplification by Fluorescence in situ Hybridization on Liquid-Based Cervical Samples: Comparison with Human Papillomavirus-DNA Testing and Histopathology

Clinical Role of the Detection of Human Telomerase RNA Component Gene Amplification by Fluorescence in situ Hybridization on Liquid-Based Cervical Samples: Comparison with Human Papillomavirus-DNA Testing and Histopathology

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

Methylated ZNF582 gene as a marker for triage of women with Pap smear reporting low-grade squamous intraepithelial lesions — A Taiwanese Gynecologic Oncology Group (TGOG) study

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