{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:48:24Z","timestamp":1760298504504},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diagn Pathol"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The amplification of oncogenes initiated by high-risk human papillomavirus (HPV) infection is an early event in cervical carcinogenesis and can be used for cervical lesion diagnosis. We measured the genomic amplification rates and the patterns of human telomerase RNA gene (TERC) and C-MYC in the liquid-based cytological specimens to evaluate the diagnostic characteristics for the detection of high-grade cervical lesions.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Two hundred and forty-three residual cytological specimens were obtained from outpatients aged 25 to 64 years at Qilu Hospital, Shandong University. The specimens were evaluated by fluorescence in situ hybridization (FISH) using chromosome probes to TERC (3q26) and C-MYC (8q24). All of the patients underwent colposcopic examination and histological evaluation. A Chi-square test was used for categorical data analysis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In the normal, cervical intraepithelial neoplasia grade 1 (CIN1), grade 2 (CIN2), grade 3 (CIN3) and squamous cervical cancer (SCC) cases, the TERC positive rates were 9.2%, 17.2%, 76.2%, 100.0% and 100.0%, respectively; the C-MYC positive rates were 20.7%, 31.0%, 71.4%, 81.8% and 100.0%, respectively. The TERC and C-MYC positive rates were higher in the CIN2+ (CIN2, CIN3 and SCC) cases than in the normal and CIN1 cases (<jats:italic>p<\/jats:italic> &lt; 0.01). Compared with cytological analysis, the TERC test showed higher sensitivity (90.0% vs. 84.0%) and higher specificity (89.6% vs. 64.3%). The C-MYC test showed lower sensitivity (80.0% vs. 84.0%) and higher specificity (77.7% vs. 64.3%). Using a cut-off value of 5% or more aberrant cells, the TERC test showed the highest combination of sensitivity and specificity. The CIN2+ group showed more high-level TERC gene copy number (GCN) cells than did the normal\/CIN1 group (<jats:italic>p<\/jats:italic> &lt; 0.05). For C-MYC, no significant difference between the two histological categories was detected (<jats:italic>p<\/jats:italic> &gt; 0.05).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The TERC test is highly sensitive and is therefore suitable for cervical cancer screening. The C-MYC test is not suitable for cancer screening because of its lower sensitivity. The amplification patterns of TERC become more diverse and complex as the severity of cervical diseases increases, whereas for C-MYC, the amplification patterns are similar between the normal\/CIN1 and CIN2+ groups.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Virtual slides<\/jats:title>\n            <jats:p>The virtual slide(s) for this article can be found here: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.diagnosticpathology.diagnomx.eu\/vs\/1308004512669913\" ext-link-type=\"uri\">http:\/\/www.diagnosticpathology.diagnomx.eu\/vs\/1308004512669913<\/jats:ext-link>.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1746-1596-7-40","type":"journal-article","created":{"date-parts":[[2012,4,13]],"date-time":"2012-04-13T16:14:28Z","timestamp":1334333668000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Genomic amplification patterns of human telomerase RNA gene and C-MYC in liquid-based cytological specimens used for the detection of high-grade cervical intraepithelial neoplasia"],"prefix":"10.1186","volume":"7","author":[{"given":"Shaomin","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunbo","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baoxia","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youzhong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beihua","family":"Kong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,4,13]]},"reference":[{"key":"546_CR1","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1126\/science.2537532","volume":"243","author":"N Dyson","year":"1989","unstructured":"Dyson N, Howley PM, M\u00fcnger K, Harlow E: The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science. 1989, 243: 934-937. 10.1126\/science.2537532.","journal-title":"Science"},{"key":"546_CR2","doi-asserted-by":"crossref","first-page":"4099","DOI":"10.1002\/j.1460-2075.1989.tb08594.x","volume":"8","author":"K M\u00fcnger","year":"1989","unstructured":"M\u00fcnger K, Werness BA, Dyson N, Phelps WC, Harlow E, Howley PM: Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product. EMBO J. 1989, 8: 4099-4105.","journal-title":"EMBO J"},{"key":"546_CR3","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1016\/0092-8674(90)90409-8","volume":"63","author":"M Scheffner","year":"1990","unstructured":"Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM: The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell. 1990, 63: 1129-1136. 10.1016\/0092-8674(90)90409-8.","journal-title":"Cell"},{"key":"546_CR4","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1002\/ijc.10627","volume":"101","author":"A Zhang","year":"2002","unstructured":"Zhang A, M\u00e5n\u00e9r S, Betz R, Angstr\u00f6m T, Stendahl U, Bergman F, Zetterberg A, Wallin KL: Genetic alterations in cervical carcinomas:frequent low-level amplifications of oncogenes are associated with human papillomavirus infection. Int J Cancer. 2002, 101: 427-433. 10.1002\/ijc.10627.","journal-title":"Int J Cancer"},{"key":"546_CR5","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1002\/(SICI)1098-2264(199708)19:4<233::AID-GCC5>3.0.CO;2-Y","volume":"19","author":"K Heselmeyer","year":"1997","unstructured":"Heselmeyer K, Macville M, Schr\u00f6ck E, Blegen H, Hellstr\u00f6m AC, Shah K, Auer G, Ried T: Advanced-stage cervical carcinomas are defined by a recurrent pattern of chromosomal aberrations revealing high genetic instability and a consistent gain of chromosome arm 3q. Genes Chromosomes Cancer. 1997, 19: 233-240. 10.1002\/(SICI)1098-2264(199708)19:4<233::AID-GCC5>3.0.CO;2-Y.","journal-title":"Genes Chromosomes Cancer"},{"key":"546_CR6","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1002\/(SICI)1098-2264(199902)24:2<144::AID-GCC7>3.0.CO;2-9","volume":"24","author":"M Kirchhoff","year":"1999","unstructured":"Kirchhoff M, Rose H, Petersen BL, Maahr J, Gerdes T, Lundsteen C, Bryndorf T, Kryger-Baggesen N, Christensen L, Engelholm SA, Philip J: Comparative genomic hybridization reveals a recurrent pattern of chromosomal aberrations in severe dysplasia\/carcinoma in situ of the cervix and in advanced-stage cervical carcinoma. Genes Chromosomes Cancer. 1999, 24: 144-150. 10.1002\/(SICI)1098-2264(199902)24:2<144::AID-GCC7>3.0.CO;2-9.","journal-title":"Genes Chromosomes Cancer"},{"key":"546_CR7","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1073\/pnas.93.1.479","volume":"93","author":"K Heselmeyer","year":"1996","unstructured":"Heselmeyer K, Schr\u00f6ck E, du Manoir S, Blegen H, Shah K, Steinbeck R, Auer G, Ried T: Gain of chromosome 3q defines the transition from severe dysplasia to invasive carcinoma of the uterine cervix. Proc Natl Acad Sci USA. 1996, 93: 479-484. 10.1073\/pnas.93.1.479.","journal-title":"Proc Natl Acad Sci USA"},{"key":"546_CR8","first-page":"#5743","volume":"46","author":"K Umayahara","year":"2005","unstructured":"Umayahara K, Hirai Y, Sugiyama Y, Takeshima N, Kato T, Takizawa K, Hasumi K, Kato H: Genetic alterations during the progression of early cervical neoplasm[abstract]. Proc Amer Assoc Cancer Res. 2005, 46: #5743-","journal-title":"Proc Amer Assoc Cancer Res"},{"key":"546_CR9","doi-asserted-by":"publisher","first-page":"3878","DOI":"10.1158\/0008-5472.CAN-04-0009","volume":"64","author":"N Wentzensen","year":"2004","unstructured":"Wentzensen N, Vinokurova S, von Knebel Doeberitz M: Systematic review of genomic integration sites of human papillomavirus genomes in epithelial dysplasia and invasive cancer of the female lower genital tract. Cancer Res. 2004, 64: 3878-3884. 10.1158\/0008-5472.CAN-04-0009.","journal-title":"Cancer Res"},{"key":"546_CR10","doi-asserted-by":"crossref","first-page":"4534","DOI":"10.1128\/jvi.65.8.4534-4538.1991","volume":"65","author":"J Couturier","year":"1991","unstructured":"Couturier J, Sastre-Garau X, Schneider-Maunoury S, Labib A, Orth G: Integration of papillomavirus DNA near myc genes in genital carcinomas and its consequences for proto-oncogene expression. J Virol. 1991, 65: 4534-4538.","journal-title":"J Virol"},{"key":"546_CR11","doi-asserted-by":"publisher","first-page":"5985","DOI":"10.1038\/sj.onc.1209625","volume":"25","author":"M Peter","year":"2006","unstructured":"Peter M, Rosty C, Couturier J, Radvanyi F, Teshima H, Sastre-Garau X: MYC activation associated with the integration of HPV DNA at the MYC locus in genital tumors. Oncogene. 2006, 25: 5985-5993. 10.1038\/sj.onc.1209625.","journal-title":"Oncogene"},{"key":"546_CR12","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1073\/pnas.84.4.1070","volume":"84","author":"M D\u00fcrst","year":"1987","unstructured":"D\u00fcrst M, Croce CM, Gissmann L, Schwarz E, Huebner K: Papillomavirus sequences integrate near cellular oncogenes in some cervical carcinomas. Proc Natl Acad Sci USA. 1987, 84: 1070-1074. 10.1073\/pnas.84.4.1070.","journal-title":"Proc Natl Acad Sci USA"},{"key":"546_CR13","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.ygyno.2004.07.036","volume":"95","author":"N Bhattacharya","year":"2004","unstructured":"Bhattacharya N, Singh RK, Mondal S, Roy A, Mondal R, Roychowdhury S, Panda CK: Analysis of molecular alterations in chromosome 8 associated with the development of uterine cervical carcinoma of Indian patients. Gynecol Oncol. 2004, 95: 352-362. 10.1016\/j.ygyno.2004.07.036.","journal-title":"Gynecol Oncol"},{"key":"546_CR14","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1038\/6010","volume":"21","author":"KJ Wu","year":"1999","unstructured":"Wu KJ, Grandori C, Amacker M, Simon-Vermot N, Polack A, Lingner J, Dalla-Favera R: Direct activation of TERT transcription by c-MYC. Nat Genet. 1999, 21: 220-224. 10.1038\/6010.","journal-title":"Nat Genet"},{"key":"546_CR15","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1186\/1471-2407-10-432","volume":"10","author":"FA Policht","year":"2010","unstructured":"Policht FA, Song M, Sitailo S, O'Hare A, Ashfaq R, Muller CY, Morrison LE, King W, Sokolova IA: Analysis of genetic copy number changes in cervical disease progression. BMC Cancer. 2010, 10: 432-10.1186\/1471-2407-10-432.","journal-title":"BMC Cancer"},{"key":"546_CR16","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4612-2042-8","volume-title":"The Bethesda system for reporting cervical cytology: definitions, criteria and explanatory notes","author":"D Solomon","year":"2004","unstructured":"Solomon D, Nayar R: The Bethesda system for reporting cervical cytology: definitions, criteria and explanatory notes. 2004, New York: Springer Science + Business Media, LLC"},{"key":"546_CR17","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.cancergencyto.2009.01.004","volume":"191","author":"Z Tu","year":"2009","unstructured":"Tu Z, Zhang A, Wu R, Jiang J, Li Y, Wulan N, Li J, Zhang Y, Li Y, Chen Z, Wei L: Genomic amplification of the human telomerase RNA gene for differential diagnosis of cervical disorders. Cancer Genet Cytogenet. 2009, 191: 10-16. 10.1016\/j.cancergencyto.2009.01.004.","journal-title":"Cancer Genet Cytogenet"},{"key":"546_CR18","doi-asserted-by":"publisher","first-page":"808","DOI":"10.2353\/jmoldx.2010.100021","volume":"12","author":"J Jiang","year":"2010","unstructured":"Jiang J, Wei LH, Li YL, Wu RF, Xie X, Feng YJ, Zhang G, Zhao C, Zhao Y, Chen Z: Detection of TERC amplification in cervical epithelial cells for the diagnosis of high-grade cervical lesions and invasive cancer: a multicenter study in China. J Mol Diagn. 2010, 12: 808-817. 10.2353\/jmoldx.2010.100021.","journal-title":"J Mol Diagn"},{"key":"546_CR19","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1093\/jnci\/djn044","volume":"100","author":"AC Rodr\u00edguez","year":"2008","unstructured":"Rodr\u00edguez AC, Schiffman M, Herrero R, Wacholder S, Hildesheim A, Castle PE, Solomon D, Burk R, the Proyecto Epidemiol\u00f3gico Guanacaste Group: Rapid clearance of human papillomavirus and implications for clinical focus on persistent infections. J Natl Cancer Inst. 2008, 100: 513-517. 10.1093\/jnci\/djn044.","journal-title":"J Natl Cancer Inst"},{"key":"546_CR20","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/j.ajog.2008.06.033","volume":"199","author":"MI Rosa","year":"2008","unstructured":"Rosa MI, Fachel JM, Rosa DD, Medeiros LR, Igansi CN, Bozzetti MC: Persistence and clearance of human papillomavirus infection: a prospective cohort study. Am J Obstet Gynecol. 2008, 199: 617-","journal-title":"Am J Obstet Gynecol"},{"key":"546_CR21","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1136\/jcp.56.7.532","volume":"56","author":"G Gallo","year":"2003","unstructured":"Gallo G, Bibbo M, Bagella L, Zamparelli A, Sanseverino F, Giovagnoli MR, Vecchione A, Giordano A: Study of viral integration of HPV-16 in young patients with LSIL. J Clin Pathol. 2003, 56: 532-536. 10.1136\/jcp.56.7.532.","journal-title":"J Clin Pathol"},{"key":"546_CR22","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1136\/jcp.2004.024570","volume":"59","author":"SM Kulmala","year":"2006","unstructured":"Kulmala SM, Syrj\u00e4nen SM, Gyllensten UB, Shabalova IP, Petrovichev N, Tosi P, Syrj\u00e4nen KJ, Johansson BC: Early integration of high copy HPV16 detectable in women with normal and low grade cervical cytology and histology. J Clin Pathol. 2006, 59: 513-517. 10.1136\/jcp.2004.024570.","journal-title":"J Clin Pathol"},{"key":"546_CR23","volume-title":"Comprehensive cervical cancer control: a guide to essential practice","author":"World Health Organization, Department of Reproductive Health and Research and Department of Chronic Diseases and Health Promotion","year":"2006","unstructured":"World Health Organization, Department of Reproductive Health and Research and Department of Chronic Diseases and Health Promotion: Comprehensive cervical cancer control: a guide to essential practice. 2006, Geneva"},{"key":"546_CR24","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/j.ajog.2007.07.047","volume":"197","author":"TC Wright Jr","year":"2007","unstructured":"Wright TC, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D, 2006 American Society for Colposcopy and Cervical Pathology-sponsored Consensus Conference: 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol. 2007, 197: 346-355. 10.1016\/j.ajog.2007.07.047.","journal-title":"Am J Obstet Gynecol"},{"key":"546_CR25","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1016\/S0002-9440(10)63498-0","volume":"163","author":"K Heselmeyer-Haddad","year":"2003","unstructured":"Heselmeyer-Haddad K, Janz V, Castle PE, Chaudhri N, White N, Wilber K, Morrison LE, Auer G, Burroughs FH, Sherman ME, Ried T: Detection of Genomic Amplification of the Human Telomerase Gene (TERC) in Cytologic Specimens as a Genetic Test for the Diagnosis of Cervical Dysplasia. Am J Pathol. 2003, 163: 1405-1416. 10.1016\/S0002-9440(10)63498-0.","journal-title":"Am J Pathol"},{"key":"546_CR26","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1016\/S0002-9440(10)62341-3","volume":"166","author":"K Heselmeyer-Haddad","year":"2005","unstructured":"Heselmeyer-Haddad K, Sommerfeld K, White NM, Chaudhri N, Morrison LE, Palanisamy N, Wang ZY, Auer G, Steinberg W, Ried T: Genomic Amplification of the Human Telomerase Gene (TERC) in Pap Smears Predicts the Development of Cervical Cancer. Am J Pathol. 2005, 166: 1229-1238. 10.1016\/S0002-9440(10)62341-3.","journal-title":"Am J Pathol"},{"key":"546_CR27","doi-asserted-by":"publisher","first-page":"604","DOI":"10.2353\/jmoldx.2007.070007","volume":"9","author":"I Sokolova","year":"2007","unstructured":"Sokolova I, Algeciras-Schimnich A, Song M, Sitailo S, Policht F, Kipp BR, Voss JS, Halling KC, Ruth A, King W, Underwood D, Brainard J, Morrison L: Chromosomal biomarkers for detection of human papillomavirus associated with genomic instability in epithelial cells of cervical cytology specimen. J Mol Diagn. 2007, 9: 604-611. 10.2353\/jmoldx.2007.070007.","journal-title":"J Mol Diagn"},{"key":"546_CR28","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.2353\/ajpath.2009.090122","volume":"175","author":"S Andersson","year":"2009","unstructured":"Andersson S, Sowjanya P, Wangsa D, Hjerpe A, Johansson B, Auer G, Gravitt PE, Larsson C, Wallin KL, Ried T, Heselmeyer-Haddad K: Detection of genomic amplification of the human telomerase gene TERC, a potential marker for triage of women with HPV-positive, abnormal Pap smears. Am J Pathol. 2009, 175: 1831-1847. 10.2353\/ajpath.2009.090122.","journal-title":"Am J Pathol"}],"container-title":["Diagnostic Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1746-1596-7-40.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T19:14:20Z","timestamp":1630523660000},"score":1,"resource":{"primary":{"URL":"https:\/\/diagnosticpathology.biomedcentral.com\/articles\/10.1186\/1746-1596-7-40"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,4,13]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,12]]}},"alternative-id":["546"],"URL":"https:\/\/doi.org\/10.1186\/1746-1596-7-40","relation":{},"ISSN":["1746-1596"],"issn-type":[{"value":"1746-1596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,4,13]]},"assertion":[{"value":"31 January 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 April 2012","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 April 2012","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"40"}}