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(American Journal of Pathology. 2009;175:1831-1847.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.090122

Detection of Genomic Amplification of the Human Telomerase Gene TERC, a Potential Marker for Triage of Women with HPV-Positive, Abnormal Pap Smears

Sonia Andersson*, Pavani Sowjanya{dagger}, Darawalee Wangsa{dagger}{ddagger}, Anders Hjerpe§, Bo Johansson, Gert Auer{ddagger}, Patti E. Gravitt||, Catharina Larsson**, Keng-Ling Wallin**, Thomas Ried{dagger} and Kerstin Heselmeyer-Haddad{dagger}

From the Department for Clinical Science, Intervention and Technology,* Division of Obstetrics and Gynecology, the Department of Laboratory Medicine,§ and the Division of Clinical Virology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital-Huddinge, Stockholm, Sweden; the Genetics Branch,{dagger} Center for Cancer Research, National Cancer Institute/NIH, Bethesda, Maryland; the Department of Oncology-Pathology,{ddagger} and Molecular Medicine and Surgery,** Karolinska Institutet, Karolinska University Hospital-Solna, Stockholm, Sweden; and the Johns Hopkins Bloomberg School of Public Health,|| Baltimore, Maryland

The vast majority of invasive cervical carcinomas harbor additional copies of the chromosome arm 3q, resulting in genomic amplification of the human telomerase gene TERC. Here, we evaluated TERC amplification in routinely collected liquid based cytology (LBC) samples with histologically confirmed diagnoses. A set of 78 LBC samples from a Swedish patient cohort were analyzed with a four-color fluorescence in situ hybridization probe panel that included TERC. Clinical follow-up included additional histological evaluation and Pap smears. Human papillomavirus status was available for all cases. The correlation of cytology, TERC amplification, human papillomavirus typing, and histological diagnosis showed that infection with high-risk human papillomavirus was detected in 64% of the LBC samples with normal histopathology, in 65% of the cervical intraepithelial neoplasia (CIN)1, 95% of the CIN2, 96% of the CIN3 lesions, and all carcinomas. Seven percent of the lesions with normal histopathology were positive for TERC amplification, 24% of the CIN1, 64% of the CIN2, 91% of the CIN3 lesions, and 100% of invasive carcinomas. This demonstrates that detection of genomic amplification of TERC in LBC samples can identify patients with histopathologically confirmed CIN3 or cancer. Indeed, the proportion of TERC-positive cases increases with the severity of dysplasia. Among the markers tested, detection of TERC amplification in cytological samples has the highest combined sensitivity and specificity for discernment of low-grade from high-grade dysplasia and cancer.






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Copyright © 2009 by the American Society for Investigative Pathology.