title: c-myc copy number gain is a powerful prognosticator of disease outcome in cervical dysplasia.
abstract: Cervical carcinoma develops from preneoplasia by a multistep process. Although most low-grade dysplastic lesions will regress without intervention and even high-grade changes exhibit a substantial rate of regression, a small percentage of dysplasia will progress over time. Thus, indicators are needed to estimate the biological risk and to help avoid overtreatment in women who desire to preserve fertility. In addition to the classical biomarkers, PCR-ELISA-determined HPV genotype and immunohistochemically assessed p16INK4a and Ki-67 expression, cells with integrated HPV and copy number gain of TERC and c-myc were quantified in a panel of 104 benign, intraepithelial neoplastic (CIN I, II, III) and cancerous lesions using fluorescence in situ hybridization. Optimal cut-off values were calculated; Kaplan-Meier curves and a Cox proportional hazard regression model were used to evaluate prognostic signatures. The assay reliably identified HPV integration, TERC and c-myc copy number gain as determined by comparisons with established biomarkers. All biomarker levels increased with the progression of the disease. However, only c-myc copy number gain independently prognosticated a low probability of dysplastic regression. Our results suggest that c-myc plays a key role in the process of dysplastic transformation and might thus be exploited for treatment and follow-up decision-making of cervical dysplasia.
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, 53127 Bonn, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Kübler
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, 53127 Bonn, Germany.
authors.forename: Sally
authors.initials: S
authors.lastname: Heinenberg
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, 53127 Bonn, Germany.|Evangelisches Krankenhaus, Teaching Hospital of the University of Bonn, 51465 Bergisch Gladbach, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Rudlowski
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, 53127 Bonn, Germany.
authors.forename: Mignon-Denise
authors.initials: MD
authors.lastname: Keyver-Paik
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, 53127 Bonn, Germany.
authors.forename: Alina
authors.initials: A
authors.lastname: Abramian
authors.affiliation: Institute of Pathology, Center for Integrated Oncology, University of Bonn, 53127 Bonn, Germany.|Institute of Pathology, Center for Integrated Oncology, University of Cologne, 50937 Cologne, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Merkelbach-Bruse
authors.affiliation: Institute of Pathology, Center for Integrated Oncology, University of Bonn, 53127 Bonn, Germany.|Institute of Pathology, Center for Integrated Oncology, University of Cologne, 50937 Cologne, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Büttner
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, 53127 Bonn, Germany.
authors.forename: Walther
authors.initials: W
authors.lastname: Kuhn
authors.affiliation: Institute of Pathology, Center for Integrated Oncology, University of Bonn, 53127 Bonn, Germany.Institute of Pathology, Center for Integrated Oncology, University of Cologne, 50937 Cologne, Germany.Institute of Pathology, University of Göttingen, 37075 Göttingen, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Schildhaus
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D005260:Female; D018628:Gene Dosage; D016259:Genes, myc; D005838:Genotype; D006801:Humans; D011379:Prognosis; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology