Universität zu Köln

Kuebler, Kirsten, Heinenberg, Sally, Rudlowski, Christian, Keyver-Paik, Mignon-Denise, Abramian, Alina, Merkelbach-Bruse, Sabine, Buettner, Reinhard, Kuhn, Walther and Schildhaus, Hans-Ulrich (2015). c-myc copy number gain is a powerful prognosticator of disease outcome in cervical dysplasia. Oncotarget, 6 (2). S. 825 - 836. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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Abstract

Cervical carcinoma develops from preneoplasia by a multistep process. Although most low-grade dysplastic lesions will regress without intervention and even highgrade 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 p16(INK4a) 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kuebler, Kirsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Heinenberg, Sally UNSPECIFIED UNSPECIFIED UNSPECIFIED Rudlowski, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Keyver-Paik, Mignon-Denise UNSPECIFIED UNSPECIFIED UNSPECIFIED Abramian, Alina UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkelbach-Bruse, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuhn, Walther UNSPECIFIED UNSPECIFIED UNSPECIFIED Schildhaus, Hans-Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-414513
Journal or Publication Title:	Oncotarget
Volume:	6
Number:	2
Page Range:	S. 825 - 836
Date:	2015
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TELOMERASE GENE TERC; IN-SITU HYBRIDIZATION; INTRAEPITHELIAL NEOPLASIA CIN; HUMAN-PAPILLOMAVIRUS; GENOMIC AMPLIFICATION; NATURAL-HISTORY; HPV; CARCINOMA; CANCER; PROGRESSION Multiple languages Oncology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41451