DNA methylation analysis in liquid-based cytology for cervical cancer screening
Sophia Apostolidou
Department of Gynecological Oncology, Institute for Women's Health, University College London, London WC1E 6DH, United Kingdom
Sophia Apostolidou and Richard Hadwin contributed equally to this work.
Search for more papers by this authorRichard Hadwin
Department of Gynecological Oncology, Institute for Women's Health, University College London, London WC1E 6DH, United Kingdom
Sophia Apostolidou and Richard Hadwin contributed equally to this work.
Search for more papers by this authorMatthew Burnell
Department of Gynecological Oncology, Institute for Women's Health, University College London, London WC1E 6DH, United Kingdom
Search for more papers by this authorAllison Jones
Department of Gynecological Oncology, Institute for Women's Health, University College London, London WC1E 6DH, United Kingdom
Search for more papers by this authorDonna Baff
Department of Histopathology, University College London, London WC1E 6JJ, United Kingdom
Search for more papers by this authorNitisha Pyndiah
Virus Reference Department, Centre for Infections, Health Protection Agency, Colindale, London NW9 5HT, United Kingdom
Search for more papers by this authorTim Mould
Department of Gynecological Oncology, Institute for Women's Health, University College London, London WC1E 6DH, United Kingdom
Search for more papers by this authorIan J. Jacobs
Department of Gynecological Oncology, Institute for Women's Health, University College London, London WC1E 6DH, United Kingdom
Search for more papers by this authorSimon Beddows
Virus Reference Department, Centre for Infections, Health Protection Agency, Colindale, London NW9 5HT, United Kingdom
Search for more papers by this authorGabrijela Kocjan
Department of Histopathology, University College London, London WC1E 6JJ, United Kingdom
Search for more papers by this authorCorresponding Author
Martin Widschwendter
Department of Gynecological Oncology, Institute for Women's Health, University College London, London WC1E 6DH, United Kingdom
Fax: ++44020-7380-9748.
Department of Gynecological Oncology, Institute for Women's Health, University College London, 1st Floor, Maple House, 149 Tottenham Court Road, London, W1T 7DN, United KingdomSearch for more papers by this authorSophia Apostolidou
Department of Gynecological Oncology, Institute for Women's Health, University College London, London WC1E 6DH, United Kingdom
Sophia Apostolidou and Richard Hadwin contributed equally to this work.
Search for more papers by this authorRichard Hadwin
Department of Gynecological Oncology, Institute for Women's Health, University College London, London WC1E 6DH, United Kingdom
Sophia Apostolidou and Richard Hadwin contributed equally to this work.
Search for more papers by this authorMatthew Burnell
Department of Gynecological Oncology, Institute for Women's Health, University College London, London WC1E 6DH, United Kingdom
Search for more papers by this authorAllison Jones
Department of Gynecological Oncology, Institute for Women's Health, University College London, London WC1E 6DH, United Kingdom
Search for more papers by this authorDonna Baff
Department of Histopathology, University College London, London WC1E 6JJ, United Kingdom
Search for more papers by this authorNitisha Pyndiah
Virus Reference Department, Centre for Infections, Health Protection Agency, Colindale, London NW9 5HT, United Kingdom
Search for more papers by this authorTim Mould
Department of Gynecological Oncology, Institute for Women's Health, University College London, London WC1E 6DH, United Kingdom
Search for more papers by this authorIan J. Jacobs
Department of Gynecological Oncology, Institute for Women's Health, University College London, London WC1E 6DH, United Kingdom
Search for more papers by this authorSimon Beddows
Virus Reference Department, Centre for Infections, Health Protection Agency, Colindale, London NW9 5HT, United Kingdom
Search for more papers by this authorGabrijela Kocjan
Department of Histopathology, University College London, London WC1E 6JJ, United Kingdom
Search for more papers by this authorCorresponding Author
Martin Widschwendter
Department of Gynecological Oncology, Institute for Women's Health, University College London, London WC1E 6DH, United Kingdom
Fax: ++44020-7380-9748.
Department of Gynecological Oncology, Institute for Women's Health, University College London, 1st Floor, Maple House, 149 Tottenham Court Road, London, W1T 7DN, United KingdomSearch for more papers by this authorAbstract
Cervical cancer is the second most common type of cancer in women worldwide. Preinvasive disease can be detected by cervical cytology. All currently available cytology technologies rely on the visual analysis of exfoliated cells from the uterine cervix. Improvement of conventional cytological screening has been proposed by the introduction of molecular-based markers applied to liquid-based cytology (LBC), the suspension of cells collected from the cervix. DNA methylation changes occur very early in carcinogenesis and identification of appropriate DNA methylation markers in such samples should be able to distinguish high-grade squamous intraepithelial lesions (HSIL) from nonspecific cytology changes and the normal cervix. To address this potential, we have undertaken a proof-of-principle study of methylation status of LBC samples from HSIL cytology cases compared against matched normal controls. Using quantitative methylation-specific PCR on 28 genes, we found SOX1, HOXA11 and CADM1 to significantly discriminate between the groups analyzed (p < 0.01). Area under the receiver operating characteristic (ROC) curve (AUC) demonstrated that methylation of SOX1, HOXA11 and CADM1 could discriminate between HSIL cases and controls with high sensitivity and specificity (AUC 0.910, 0.844 and 0.760, respectively). The results were further validated in an independent set. This proof-of-principle study is the first to validate the results in an independent case/control set and presents HOXA11, a gene that is important for cervical development, as a potentially useful DNA marker in LBC samples. Further assessment of these preliminary estimates will need to be performed in a larger cohort to confirm clinical utility. © 2009 UICC
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