hTERC Gene Amplification Research Articles

Study on the correlation between hTREC and HPV load and cervical CINI/II/III lesions and cervical cancer.

ObjectiveTo investigate the correlation between hTREC and human papillomavirus (HPV) load and cervical intraepithelial neoplasia (CIN) grade II/III lesions and cervical cancer.MethodsA total of 135 patients with cervical lesions of different degrees admitted to our hospital from January 2016 to February 2017 were selected, including CIN I/III 65 cases, grade III 39 cases, and cervical cancer 31 cases. The expression of hTERC gene was detected by fluorescence in situ hybridization (FISH) in three groups, and the HPV load was detected by second‐generation hybridization capture (HC II) method, and its relationship with cervical lesion grade was analyzed. Department.ResultsThe positive expression rate of hTERC gene amplification was cervical cancer > CIN I/II lesion > CIN III lesion; the positive expression rate of HPV was cervical cancer > CIN I/II lesion > CIN III lesion. After treatment, the positive rate of hTERC gene amplification and HPV expression decreased significantly within 1 year (P < .05). Spearman's analysis showed that the degree of cervical lesion was positively correlated with hTREC and HPV load (P < .05).ConclusionhTREC and HPV are closely related to the occurrence and development of cervical precancerous lesions and cervical cancer. The abnormal amplification of hTERC gene increases with the grade of cervical lesions. Both of them can be used as auxiliary indicators for early screening, treatment, and prognosis of cervical cancer.

HPV16 E6/E7 upregulate hTERC mRNA and gene amplification levels by relieving the effect of LKB1 on Sp1 phosphorylation in lung cancer cells.

Background:There is an immediate need for research on the mechanism underlying telomerase activation and overexpression.Materials & Methods:A total of 174 patients with lung cancer (n = 106) and benign lung disease (n = 68) were recruited for the current study. The mRNA expression levels of E6, E7, LKB1, Sp1, and hTERC in brushing cells were detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and hTERC amplification was also detected by fluorescence in situ hybridization (FISH). To investigate the potential mechanism, bidirectional genetic manipulation was performed in well-established lung cancer cell lines.Results:Our results indicated that the mRNA expression levels of E6, E7, Sp1, and hTERC and the amplification level of hTERC were significantly increased in the malignant group compared with those of the benign group (p < 0.01). Conversely, the mRNA expression level of LKB1 was significantly decreased in the malignant group (p < 0.01). The correlation between E6, E7, Sp1, and hTERC expression was positive but was negative with LKB1 (p < 0.01). Our results also showed that HPV16 E6/E7 downregulated the expression of LKB1 at both the protein and mRNA levels. The loss of LKB1 upregulated Sp1 expression, and also promoted Sp1 activity. Sp1 further upregulated hTERC at the mRNA and gene amplification levels. Thus, we proposed a HPV–LKB1–Sp1–hTERC axis of E6/E7 upregulation of hTERC expression.Conclusion:We demonstrated for the first time that E6 and E7 promoted hTERC mRNA expression and the amplification of hTERC by relieving the effect of LKB1 on the phosphorylation of Sp1. Sp1 further activated hTERC by directly binding to the promoter regions of hTERC.

Human papillomavirus and human telomerase RNA component gene in cervical cancer progression

This study aimed to examine hTERC gene in different grades of cervical intraepithelial neoplasia (CIN) and cervical cancer, and the association between hTERC and high risk-human papillomavirus (HR-HPV) infection. Patients who underwent cervical cancer screening at the Second Affiliated Hospital of Kunming Medical University between October 2010 and December 2011 were enrolled. All patients underwent liquid-based cytology test and hybrid capture 2 (HC2) for HPV detection. hTERC was examined using fluorescence in situ hybridization (FISH). Cervical colposcopy biopsy was performed if any of the three results was positive. HC2, FISH, and pathology were compared. A total of 1200 women underwent screening, 150 patients underwent cervical biopsy: 32 in the normal group, 38 in the CIN1 group, 66 in the CIN2/3 group, and 14 in the invasive cervical cancer group. More patients had HR-HPV infection in the CIN2/3 group and ICC group compared with the CIN1 group. hTERC increased with increasing histological dysplasia. There was significant difference in hTERC positive rate between each of the three groups. More patients with hTERC gene amplification were observed in the positive HR-HPV group than in the HR-HPV negative group. In conclusion, hTERC is a potential marker for precancerous cervical cancer lesions. hTERC might be correlated with HR-HPV infection in cervical diseases.

Establishment and analysis of the prediction model for cervical squamous cell carcinoma.

This study aimed to construct a prediction model for cervical squamous cell carcinoma and evaluate its accuracy in diagnosing cervical squamous cell carcinoma. Fifty patients with initially histopathologically confirmed cervical squamous cell carcinoma and 150 patients with initially histopathologically confirmed cervical intraepithelial neoplasia (CIN) were enrolled. The high-risk human papillomavirus (HR-HPV) infection, human telomerase mRNA component (hTERC) gene and cell-myc (c-myc) gene amplification, and minichromosome maintenance protein 5 (MCM5) protein expression were detected. The indicators related to cervical cancer were screened. The regression model was established to predict cervical squamous cell carcinoma with backward logistic stepwise regression method, and the accuracy of the model was evaluated. Histograms for HR-HPV infection and viral load, hTERC and c-myc gene amplification, and MCM5 protein expression were constructed. There was a linear relationship between hTERC (X1), HR-HPV viral load (X2), MCM5 (X5) and the regression equation. Also, hTERC (X1), HR-HPV viral load (X2) and MCM5 (X5) were correlated with cervical squamous cell carcinoma. The regression model Logit (p) = -66.283 + 0.042 X1 + 0.061 X2 + 0.052 X5 was established. The model-fitting effect and prediction accuracy were evaluated, HL test p = 1 (p > 0.05). The model fitting effect was good, Cox-Sn ell R2 was 0.643 and Nagelkerke R2 was 0.958. The high accuracy of the model was 98.5%. The fitting-effect of the regression model established by hTERC gene expression, HR-HPV viral load and MCM5 protein was good. The prediction accuracy of the model for cervical squamous cell carcinoma was high. The combined test of hTERC gene amplification, HR-HPV viral load and MCM5 protein could be used to predict and evaluate cervical squamous cell carcinoma.

Application of Van-Clear and xylene in the detection of cervical hTERC gene by fluorescence in situ hybridization

To observe the effect of Van-Clear on vamplification of human telomerase RNA component (hTERC) gene in cervical tissues by fluorescence in situ hybridization, and to determine the potential for Van-Clear to replace xylene. A total of 278 specimens of cervix uteri were collected from inpatients of Department of Gynaecology in Boai Hospital of Zhongshan from January to February, 2015, with 81 cases of normal specimens, 68 cases of cervical intraepithelial neoplasia (CIN) I, 57cases of CIN2, 42 cases of CIN3 and 30 cases of cervical invasive cancer. Double samples were collected from the same region. Fluorescence in situ hybridization was applied to detect the changes in the amplification of hTERC gene in 2 groups of specimens from the cervical biopsy. Differences in the positive expression rate of hTERC gene between the 2 groups of cervical lesions at all levels were not statistically significant (P>0.05). There is no significant difference in the positive rate of hTERC gene expression between the slices made by Van-clear and xylene. As an environmental-friend product, Van-Clear possesses certain value in detection of cervical hTERC gene by fluorescence in situ hybridization.

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

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.

Human Telomerase Gene and High-Risk Human Papillomavirus Infection are Related to Cervical Intraepithelial Neoplasia

Our aims were to evaluate the clinical performance of human telomerase RNA gene component (hTERC gene) amplification assay with high-risk human papillomavirus (HR-HPV) DNA test of Hybrid Capture 2 DNA test (HC2), for the detection of high grade cervical precancerous lesions and cancer (CIN 2+). In addition, the association shown between hTERC gene amplification and HPV DNA test positive in women with and without cervical neoplasia was assessed. There were 92 women who underwent cytology, HR-HPV DNA test, hTERC gene amplification test, colposcopy and biopsy. We compared the clinical performance of hTERC gene test along with HR-HPV DNA test of women with colposcopy and routine screening. The samples were histology- confirmed high-grade cervical intraepithelial neoplasia (CIN 2) or worse (CIN2+) as the positive criterion. The test of hTERC gene showed the hTERC gene amplification positivity increased with the severity of histological abnormality and cytological abnormality. The test of hTERC gene showed higher specificity than HR-HPV DNA test for high-grade lesions (84.4% versus 50%) and also higher positive predictive value (90.4% versus 76.5%). Our results predicted that hTERC gene amplification demonstrated more specific performance for predicting the risk of progression and offer a strong potential as a tool for triage in cervical cancer screening, with the limited sensitive as HR-HPV DNA test.

ATL

To investigate the clinical significance of abnormal human telomerase RNA gene component (hTERC) gene amplification tested by fluorescence in situ hybridization in cervical lesions. In 373 patients with cytologic abnormalities, high-risk human papilomavirus (HR-HPV) was detected by the hybrid capture II method, and abnormal amplification of the hTERC gene in exfoliated cells was detected by fluorescence in situ hybridization. Cell smear findings suggested atypical squamous cells in 148 patients, low-grade squamous intraepithelial lesion in 62 patients, and high-grade squamous intraepithelial lesion in 107 patients, squamous cell carcinoma in 56 patients, and cervical biopsy-revealed inflammation in 89 patients, cervical intraepithelial neoplasia (CIN) I in 36 patients, CIN II in 43 patients, CIN III in 129 patients, and infiltrating carcinoma in 76 patients. In the inflammation, CIN I, CIN II, CIN III, and infiltrating carcinoma groups, the infection rates of HR-HPV were 29.21%, 52.78%, 74.42%, 92.25%, and 93.42% (P < 0.01), respectively; the positive rates of hTERC gene amplification were 0.00%, 13.89%, 41.86%, 78.29%, and 89.47% (P < 0.01), respectively. With respect to advanced cervical lesions (≥CIN II), cytology (≥ low-grade squamous intraepithelial lesion), HR-HPV testing, and hTERC testing differed insignificantly in the negative predictive value (P > 0.05), but they differed significantly in the sensitivity, specificity, and positive predictive value (P < 0.01). Among the 3 methods, hTERC testing showed the highest specificity and positive predictive value, and HR-HPV testing showed the highest sensitivity. In 41 patients with untreated CIN I and CIN II, the sensitivity of detection of hTERC gene amplification to predict lesion progression was 88.89%, and the specificity was 93.75%. Detection of abnormal amplification of the hTERC gene can assist in screening cervical lesions and identifying CIN I/II patients with a high progression risk.

Clinical significance of combined detection of human papilloma virus infection and human telomerase RNA component gene amplification in patients with squamous cell carcinoma of the esophagus in northern China

BackgroundThe aim of the study was to test for human papilloma virus (HPV) infection and human telomerase RNA component (hTERC) gene amplification in tissues derived from esophageal cancer, in esophagus displaying atypical hyperplasia and in normal tissue, and to analyze the relationship between them and discuss whether HPV infection and hTERC gene amplification play a role in the duration of survival of esophageal cancer patients.MethodsTo test for HPV infection, surface plasma resonance was used after extracting and subjecting the DNA to PCR amplification. Measurement of hTERC gene amplification was performed by the fluorescence in situ hybridization technique.ResultsThe rates of HPV infection in the normal group, the atypical esophageal hyperplasia group and the cancer group were 0% (0/40), 10.00% (1/10) and 20.65% (19/92), respectively, with a statistically significant difference of P < 0.01. The hTERC gene amplification rate in normal tissue, grade I atypical hyperplastic tissue, grade II/III atypical hyperplastic tissue and esophageal cancer tissue were 0% (0/89), 15.38% (4/26), 47.06% (8/17) and 89.13% (82/92), respectively, with a statistically significant difference of P < 0.01. On follow-up of 92 patients, survival curves of the HPV-positive and HPV-negative groups were not significantly different (P > 0.05). Survival curves of the hTERC gene amplification-positive and hTERC gene amplification-negative groups were statistically significant (P < 0.05). A matching chi-square test showed that there was no correlation between HPV infection and hTERC gene amplification (P > 0.05).ConclusionHPV infection may be one of many factors contributing to the development of esophageal cancer, but it does not influence prognosis. Amplification of the hTERC gene appears to influence certain features associated with postoperative survival in esophageal carcinoma patients.

Morphology, immunohistochemistry and hTERC gene in-situ hybridization in Barrett's esophagus

To study the clinicopathologic features and differential diagnosis of proximal gastric mucosa and mucosa of Barrett's esophagus (BE) in biopsy specimens. Thirty-eight cases of Barrett's esophagus (diagnosed using WHO criteria) and 44 cases of proximal gastric mucosa were studied by immunohistochemistry (for CK7, CK20, CK4, CK8, S-100 protein, MUC6, COX2 and bcl-2) and fluorescence in-situ hybridization (FISH) (for hTERC gene). The pathologic features were analyzed. The differences in expression of CK7, CK20, MUC6, COX2 and bcl-2 between BE and proximal gastric mucosa with intestinal metaplasia were not statistically significant (P > 0.05). There was however a statistically significant difference in expression of S-100 protein (P < 0.05). The expression of CK7/CK4 and CK7/CK8 in BE showed positive correlation (P < 0.05). However, such correlation was not demonstrated in proximal gastric mucosa (P > 0.05). The results of hTERC gene expression by FISH showed a statistically significant difference between the two groups: 57.9% (22/38) in BE and 13.6% (6/44) in proximal gastric mucosa (P < 0.05). The significance of CK7 and CK20 expression is uncertain in the differential diagnosis between BE and proximal gastric mucosa. On the other hand, positivity for CK7/CK4/CK8 may support the diagnosis of BE and play a role in distinguishing between the two groups. S-100 protein expression and detection of hTERC gene amplification also contribute to the diagnosis of BE.

Genomic amplification of the human telomerase gene (hTERC) associated with human papillomavirus is related to the progression of uterine cervical dysplasia to invasive cancer

BackgroundHuman papillomavirus (HPV) infection plays an etiological role in the development of cervical dysplasia and cancer. Amplification of human telomerase gene (hTERC) and over expression of telomerase were found to be associated with cervical tumorigenesis. This study was performed to analyze genomic amplification of hTERC gene, telomerase activity in association with HPV infection in different stages of cervical intraepithelial neoplasia (CIN) and cervical cancer. We were studying the role of hTERC in the progression of uterine cervical dysplasia to invasive cancer, and proposed an adjunct method for cervical cancer screening.MethodsExfoliated cervical cells were collected from 114 patients with non neoplastic lesion (NNL, n=27), cervical intraepithelial neoplasia (CIN1, n=26, CIN2, n=16, CIN3, n=24) and cervical carcinoma (CA, n=21), and analyzed for amplification of hTERC with two-color fluorescence in situ hybridization (FISH) probe and HPV-DNA with Hybrid Capture 2.From these patients, 53 were taken biopsy to analyze telomerase activity by telomeric repeat amplification protocol (TRAP) and expression of human telomerase reverse transcriptase (hTERT), with immunohistochemistry (IHC). All biopsies were clinically confirmed by phathologists.ResultsAmplification of hTERC was significantly associated with the histologic diagnoses (p<0.05). The positive correlation was found between the level of hTERC amplification and histologic grading of dysplasia (CIN2/3 from CIN1 or normal, P=0.03). A profounding increase in the accumulation of HPV and hTERC positive cases was observed in the CIN3 subgroup compared with the CIN2 group, 25% versus 62.96%, respectively (p=0.007).ConclusionshTERC ampliffication can be detected with FISH technique on exfoliated cervical cells. Amplification of hTERC and HPV infection are associated with more progressive CIN3 and CA. The testing of hTERC amplification might be a supplementary to cytology screening and HPV test, especially high-risk patients.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1857134686755648.

Human telomerase RNA component (hTERC) gene amplification detected by FISH in precancerous lesions and carcinoma of the larynx

BackgroundGain of 3q26 is frequently observed in squamous cell carcinomas of mucosal origin, including those originating in the head and neck region. The human telomerase RNA component (hTERC) gene, which is located on chromosome 3q26, encodes for an RNA subunit of telomerase that maintains the length of telomeres through cellular divisions, and is activated in malignant diseases. The present study was designed to detect hTERC amplification in laryngeal lesions and evaluate whether this might serve as a supportive biomarker in histopathological analysis for in the diagnosis of laryngeal lesions.MethodsFluorescent in situ hybridization (FISH) was applied on formalin-fixed paraffin-embedded blocks of 93 laryngeal specimens, including 14 normal epithelium (NE), 15 mild dysplasia (Md), 18 moderate dysplasia (MD), 16 severe dysplasia (SD), 9 carcinoma in situ (CIS), and 21 invasive carcinoma (IC)).ResultsBy histopathologic examination, hTERC amplification rates in NE, Md, MD, SD, CIS and IC cases were 0% (0/14), 13.33% (2/15), 72.22% (13/18), 81.25% (13/16), 100% (9/9) and 100% (21/21), respectively. Amplification of hTERC was significantly associated with histopathologic diagnosis (P < 0.0001). The percentage of hTERC amplification in patients with MD, SD, CIS, and IC was significantly higher than those with NE or Md (P < 0.0001). The number of cells with abnormal signals increased and the abnormal signal patterns were diversified with increasing severity of laryngeal dysplasia (P < 0.0001).ConclusionsThe hTERC amplification is important in the development of laryngeal squamous cell carcinoma (LSCC). FISH detection of hTERC amplification may provide an effective approach in conjunction with histopathologic evaluation for differential diagnosis of laryngeal lesions.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2226606266791985

HTERC gene amplification and expression of human papillomavirus in cervical carcinogenesis

宫颈癌作为威胁女性生命的恶性肿瘤,其发生和细胞异常凋亡与高危型人乳头状瘤病毒( HPV)感染密切相关.人端粒酶逆转录酶( hTERC)基因的扩增可激活端粒酶活性而维持端粒长度,使细胞逃避凋亡而发生无限制增殖,进而发生癌变.HPV感染可致细胞DNA发生突变而致癌.我们分析了hTERC基因扩增和高危型HPV感染在宫颈上皮癌变过程中的意义及相关性,以期为临床早诊早治、监测病情和评估预后提供一定的科学依据。

Cervical cancer screening: hTERC gene amplification detection by FISH in comparison with conventional methods

Aim: To assess the clinical significance of hTERC amplification for cervical cancer screening detected by fluorescence in situ hybridization (FISH) and compare it with that of current screening methods within the same group. Methods: A total of one hundred and nine women were recruited in this study. All of them had liquid-based thin-prep cytologic test (TCT), human papillomavirus (HPV) DNA testing and hTERC gene amplification analysis using interphase two-color FISH. In addition, colposcopically directed biopsy and/or cone biopsy were conducted for definite histopathologic diagnosis for each case. The optimal threashold of hTERC gene amplification by fluorescence in situ hybridization (FISH) were assecced by receiver operating characteristic (ROC) curve. The results of hTERC gene amplification analysis were compared with the cytological analysis, HPV DNA testing and those of subsequent biopsies. Results: Among the 109 patients, 18 were benign lesion, 17 were LSIL, 66 were HSIL and 8 were invasive carcinoma of cervix (ICC). Of them, hTERC-positive cases were found in 0.0% (0/18) of normal specimens, 11.8% (2/17) of LSIL, 72.7% (48/66) of HSIL and 100.0% (8/8) of ICC, respectively. The positive rate of hTERC gene amplification was significantly higher in HSIL and ICC compared with normal and LSIL (all P < 0.01).The optimal cut-off point of percentages of cells with hTERC amplification was determined as 5.5%. Using this threshold the hTERC test reached a much higher specificity(94.3%, 33/35) and a relatively lower sensitivity(77.0%, 57/74) to distinguish benign lesion and LSIL from HSIL and ICC in comparison with HR-HPV test (51.4%; 91.9%) and TCT (74.3%; 81.1%). Area Under the Curve revealed that hTERC amplification test performed more accurately (area under the curve = 0.857) compared to HPV test (area under the curve = 0.717) and cytology(area under the curve = 0.777) to discriminate HSIL or higher from LSIL or lower. This study also found a significant positive correlation between positive hTERC gain and HR-HPV infection, abnormal cytological or histopathologic lesions (all P < 0.01) in patients with cervical diseases. Conclusion: hTERC amplification testing may be a promising adjunct to screen women for cervical precancer or cancer with high specificity and accuracy.

Expression and clinical significance of genetic amplication of the human telomerase component gene in cervical adenocarcinomas

Objective To detect the expression and clinical significance of amplification of the human telomerase component(hTERC) in the specimens of cervical adenocarcinomas and discuss the clinical significance of its normal amplification. Methods Retrospective analysis was carried out to the clinical material of 15 cervical adenocarcinomaspatients who received operation in our hospital from 2000 to 2010. Their paraffin-embedded cervical tissues were established as experimental group,15 cervical specimens of chronic cervicitis women were established as control group. All of specimens were detected by FISH to evaluate the hTERC gene amplification. Results No control group samples revealed copy number increases of 3q, while 100 ％ of cervical adenocarcinomas tissues showed extra copies of 3q. hTERC copy numbers in cervical adenocarcinomas were significantly higber than those in control group 1 samples, (P＜0.001).Conclusions hTERC gene showed abnormal amplification in the cervical adenocarcinomas. And the detection of hTERC gene amplification by FISH could help the early diagnosis of cervical adenocarcinomas. Key words: Cervical adenocarcinomas; hTERC gene; Fluorescence in situ hybridization; High risk of human papillomavirus infection

Expression of human telomerase gene in esophageal cancer

Objective To evaluate the dual-color interphase fluorescence in situ hybridization (FISH) of human telomerase gene (hTERC) in the esophageal cancer and preneoplastic lesions. Methods The fluorescence signals of hTERC in the esophageal cancer and preneoplastic lesions were detected by using interphase FISH. According to histology, biopsy and pathology certification, the samples include 45 cases of esophageal normal tissue, 27 cases of atypical hyperplasia Ⅰ , 22 cases of atypical hyperplasia Ⅱ / Ⅲ and 55 cases of squamous cell carcinomas (SCC) of the esophagus. Results None normal samples revealed copy number increases of 3q, while 25.9% of atypical hyperplasia Ⅰ , 54. 5% of atypical hyperplasia Ⅱ/Ⅲ, 90. 9% of the squamous esophageal cancer showed extra copies of 3q. The comparison between groups showed statistically significant difference ( P ＜ 0. 05 ). The mean copy number was 2. 19 ±0. 11,2. 35 ± 0. 30, 2. 64 ± 0. 27 respectively. The positive amplification of the hTERC gene was not correlated with histological stages, lymph nodes metastasis and the grades of carcinoma differentiation in SCC (P ＞ 0. 05 ). Conclusion The presence of hTERC gene may play an important role in the development of SCC. Key words: Fluorescence in situ hybridization; hTERC; Esophageal cancer

Fluorescence in situ hybridization analysis of the hTERC region in acute myeloid leukemia patients.

The telomerase RNA component (hTERC) gene is located at 3q26. Increased hTERC gene expression has been frequently observed and amplification was shown using fluorescence in situ hybridization (FISH) in different cancers. The aim of this study was to determine whether hTERC gene amplification is detectable by FISH in acute myeloid leukemia (AML) cells. FISH and karyotype results at the time of diagnosis of 23 adult AML patients were retrospectively evaluated. Additionally, fixed cells were hybridized with an hTERC region-specific FISH probe to determine gene amplification. Ten of the 23 patients had a normal karyotype and 6 had an abnormal karyotype. hTERC region amplification was not observed in any of the patients. Although it was reported that hTERC gene amplification may partially contribute to increased telomerase expression and activity in leukemic cells, it is not possible to make such a conclusion based on the results of the this study, as hTERC amplification was not observed in the study group. This suggests that increased telomerase activity via gene amplification in the development of AML may not be as important a factor as it is in solid tumors.

Detection of human telomerase RNA component gene by fluorescent in situ hybridization for screening of cervical lesions

To investigate the value of fluorescence in situ hybridization (FISH) detection of human telomerase RNA component (hTERC) gene amplification in screening of cervical lesions. A total of 146 post-thinPrep cytology test (TCT) samples were analyzed using FISH by two-color interphase probe targeting hTERC gene at chromosome 3q26 and the data were compared with the cytological and histological results. FISH analysis was successful in 120 cases (20 cases of normal and 100 abnormal cases by TCT). Gene amplification of hTERC by FISH had a positive correlation with the cytological (r = 0.465, P < 0.01) and histological grade results (r = 0.610, P < 0.01). Extra copies of hTERC were seen in 28.6% (6/21) of CINI, 61.1% (11/18) of CINII, 75.0% (18/24) of CINIII and 91.7%(22/24) of squamous cell carcinoma, respectively. None (0/13) of the inflammation cases showed hTERC amplification. The sensitivity and specificity for detecting high grade lesions by FISH were 77.3% (51/66) and 82.4% (28/34); and the positive and negative predictive values were 89.5% and 65.1%, respectively. The rate of hTERC gene gain in high grade lesions was significantly higher than that in the low grade lesions (χ(2) = 32.550, P < 0.01). Combined with the high copy numbers, the sensitivity for detecting high grade lesions was increased to 81.2%. Detection of hTERC gene amplification by FISH improves the screening efficiency of high-risk cervical epithelial lesions. The presence of high copy numbers of hTERC correlates with the presence of high grade cervical dysplasia.

Amplification of the Telomerase RNA Component Gene in the Process of Human Esophageal Carcinogenesis

Amplification of the human telomerase RNA component (hTERC) gene occurs early in cervical cancer development. Telomerase, the product of the hTERC gene, plays an important role in tumor cell apoptosis and genomic stability. Given the numerous similarities between esophageal and cervical cancers, we hypothesized that hTERC gene amplification may also be related with esophageal cancer development. We therefore examined 189 tissue sections from 63 cases of esophageal cancer and preneoplastic lesions. hTERC gene amplification in the lesions was detected by interphase fluorescence in situ hybridization. Of the 189 tissue sections, 149 were successfully evaluated (40 samples were excluded because of inappropriately preparation) and were classified as normal (n=45), atypical hyperplasia I (n=27), atypical hyperplasia II/III (n=22), and squamous cell carcinomas (SCCs; the most common type of esophageal cancer) (n=55). hTERC gene expression was not detected in normal esophageal tissue, whereas its expression was detected in atypical hyperplasias I (25.9%), atypical hyperplasia II/III (54.5%), and SCCs (90.9%) (p<0.05). The average copy numbers of hTERC in atypical hyperplasias I and II/III, as well as SCCs were 2.19, 2.35, and 2.64, respectively. In particular, the numbers of abnormal nuclei in atypical hyperplasias II/III were significantly higher than those of in atypical hyperplasia I (p<0.05). The hTERC gene amplification was not related with patient gender, histological stage, lymph nodes metastasis, and SCC differentiation grade (p>0.05). All these findings suggest that hTERC gene amplification is associated with SCC development.

O1005 The amplification and clinical significance of hTERC gene in the cervical exfoliated cells from natural population in Shenzhen

O1005 The amplification and clinical significance of hTERC gene in the cervical exfoliated cells from natural population in Shenzhen