Application of hTERC in thinprep samples with mild cytologic abnormality and HR-HPV positive
ABSTRACT Amplification of hTERC is found to be an important genetic event in the progression from cervical dysplasia to cervical cancer. The hTERC value in predicting high-grade cervical intraepithelial neoplasia (CIN) or squamous cell carcinoma (SCC), in high-risk HPV (HR-HPV) positive thinprep samples with atypical squamous cells (ASC) or a low-grade squamous intraepithelial lesion (LSIL) was explored in this study.
A total of 300 thinprep cytology specimens (129 of ASC-US, 82 of LSIL, and 89 of ASC-H) with positive HR-HPV DNA was detected by a two-probe dual-color FISH panel, targeting hTERC and the centromeric region of chromosome 3 (CSP3). Using >2 signals for hTERC together with ≥2 signals for CSP3 to define abnormal nucleus, and the cutoff value was set at 6.5 per random 200 nuclei displayed increased hTERC signals and/or tumor ploidy. Statistical analyses were based on histologic findings of colposcopy biopsies, allowing CIN2 or worse (CIN2+) as the positive criterion.
The FISH results were systematically analyzed among groups, based on histologic diagnosis, cytologic finding, HR-HPV viral load, and age status. hTERC presented good consistency with histology, and had satisfactory sensitivity, specificity, and accuracy among different groups, with less difference intergroup. The individual hTERC positive nuclei ratio was generally increased with severity of the cervical lesions.
hTERC could be a stable predictor in assuring the risk of high-grade CIN in women with mild cytologic abnormality and positive HR-HPV, and the individual positive nuclei ratio of it might be helpful in identifying morbid grade for cervical lesions.
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ABSTRACT: Background Currently the routine non-invasive screening methods for cervical intraepithelial neoplasia (CIN) and cervical cancer are Thinprep cytology test (TCT) and human papillomavirus testing. However, both methods are limited by the high false positive and false negative rates and lack of association with patients’ prognosis, especially for the early detection of pro-malignant CIN. The aim of the study was to investigate the role of genomic amplification of human telomerase gene (hTERC) in the diagnosis and prognosis of CIN. Methods The study group consisted of specimens of exfoliated cervical cells from 151 patients, including 27 with CIN I, 54 with CIN II/III, 17 with carcinoma in situ, and 28 with invasive squamous carcinoma, as well as 25 patients who were at 2-year follow-up after either Loop Electrosurgical Excision treatment (n = 11) or radical surgery (n = 14). hTERC amplification was detected by dual-color interphase fluorescence in situ hybridization (FISH), and the results were compared with TCT and histologic examination. The final diagnosis was determined by the pathological examination. The control group consisted of specimens of exfoliated cervical cells from 40 normal women. Results The percentage of cervical exfoliated cells with positive hTERC amplification and incidence rates of hTERC amplification were 9.2% ± 4.6% and 44.4% (12/27) respectively in patients with CIN I; 16.0% ± 14.4% and 85.1% (46/54) in patients with CIN II/III; 19.7% ± 13.3% and 88.3% (15 /17) in patients with carcinoma in situ; 47.0% ± 25.2% and 100% (28/28)in patients with invasive squamous carcinoma. There was statistically significant difference between the control and study group (P <0.01), and between the patients with various diseases within the study group (P <0.05). Conclusion The detection of genomic amplification of hTERC using FISH is a non-invasive and effective approach for CIN.World Journal of Surgical Oncology 08/2012; 10(1):168. DOI:10.1186/1477-7819-10-168 · 1.20 Impact Factor
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ABSTRACT: Gains of 3q26 chromosome region, where the human telomerase RNA gene (hTERC) is located, have been previously documented in cervical carcinomas. However, published data on this subject are inconclusive. Therefore, we performed a meta-analysis to evaluate the diagnostic value of hTERC in high-grade cervical lesions and invasive cancer. We searched all the eligible studies through PubMed, EMBASE, and the Cochrane Library database without language limitation. Studies were assessed for quality using quality assessment of diagnostic accuracy studies (QUADAS). Positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were pooled separately and compared with overall accuracy measures of diagnostic odds ratio (DOR) and symmetric summary receiver operating characteristic (SROC). The PLR and NLR and their 95 % confidence interval (CI) were calculated using a fixed effects model according to the Mantel-Haensed method and random effects model based on the work of Der Simonian and laird, respectively. A total of 12 studies were included for the analysis. The pooled sensitivity was 0.81 (95 % CI, 0.80-0.82). The pooled specificity was 0.83 (95 % CI, 0.82-0.84). The DOR estimate was performed, and the result was 17.37. Our meta-analysis showed that the detection of genomic amplification of hTERC is a noninvasive and effective approach for high-grade cervical lesions and invasive cancer.Tumor Biology 04/2014; 35(7). DOI:10.1007/s13277-014-1915-z · 2.84 Impact Factor
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ABSTRACT: Conventional cytogenetics in conjunction with Fluorescence in Situ Hybridization (FISH) continues to remain an important and integral component in the diagnosis and management of solid tumors. The ability to effectively detect the vast majority of clinically relevant chromosomal aberrations with a rapid-to-acceptable turnaround time makes them the most cost-effective screening/detection tool currently available in modern pathology. In this review, we describe a representative set of solid tumors in which chromosomal analysis and/or FISH plays a significant role in the routine clinical management of solid tumors.Clinics in laboratory medicine 12/2011; 31(4):785-811, xi. DOI:10.1016/j.cll.2011.07.007 · 1.35 Impact Factor