c-myc copy number gain is a powerful prognosticator of disease outcome in cervical dysplasia

作者: Kirsten Kübler , Sally Heinenberg , Christian Rudlowski , Mignon-Denise Keyver-Paik , Alina Abramian

DOI: 10.18632/ONCOTARGET.2706

关键词: BioinformaticsCarcinomaBiomarker (medicine)Cervical intraepithelial neoplasiaGene dosageOncologyGenotypeDysplasiaInternal medicineDiseaseBiologyFluorescence in situ hybridization

摘要: 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 substantial rate of regression, small percentage dysplasia progress over time. Thus, indicators are needed to estimate the biological risk help avoid overtreatment in women who desire preserve fertility. In addition classical biomarkers, PCR-ELISA-determined HPV genotype immunohistochemically assessed p16INK4a Ki-67 expression, cells with integrated copy number gain TERC c-myc were quantified panel 104 benign, intraepithelial neoplastic (CIN I, II, III) cancerous using fluorescence situ hybridization. Optimal cut-off values calculated; Kaplan-Meier curves Cox proportional hazard regression model used evaluate prognostic signatures. The assay reliably identified integration, as determined comparisons established biomarkers. All biomarker levels increased progression disease. However, only independently prognosticated low probability regression. Our results suggest that plays key role process transformation might thus be exploited for treatment follow-up decision-making cervical dysplasia.

参考文章(48)
D. Zimonjic, T. Ried, H.M. Padilla-Nash, M.V.E. Macville, E. Schrock, N. Popescu, C. Keck, B.M. Ghadimi, Comprehensive and Definitive Molecular Cytogenetic Characterization of HeLa Cells by Spectral Karyotyping Cancer Research. ,vol. 59, pp. 141- 150 ,(1999)
Alberto Pacchiarotti, Francesca Ferrari, Paola Bellardini, Francesco Chini, Guido Collina, Paolo Dalla Palma, Bruno Ghiringhello, Vincenzo Maccallini, Fabio Musolino, Giovanni Negri, Roberto Pisa, Ilaria Sabatucci, Paolo Giorgi Rossi, Prognostic value of p16-INK4A protein in women with negative or CIN1 histology result: A follow-up study International Journal of Cancer. ,vol. 134, pp. 897- 904 ,(2014) , 10.1002/IJC.28407
Ellen C. Obermann, Spasenija Savic Prince, Audrey Barascud, Bruno Grilli, Michelle Herzog, Daniela Kaup, Gieri Cathomas, Brigitte Frey Tirri, Inti Zlobec, Edward Wight, Lukas Bubendorf, Prediction of outcome in patients with low-grade squamous intraepithelial lesions by fluorescence in situ hybridization analysis of human papillomavirus,TERC, andMYC Cancer Cytopathology. ,vol. 121, pp. 423- 431 ,(2013) , 10.1002/CNCY.21280
Martin Steinau, Daisy R Lee, Mangalathu S Rajeevan, Suzanne D Vernon, Mack T Ruffin, Elizabeth R Unger, Gene expression profile of cervical tissue compared to exfoliated cells: Impact on biomarker discovery BMC Genomics. ,vol. 6, pp. 64- 64 ,(2005) , 10.1186/1471-2164-6-64
Pulivarthi H Rao, Hugo Arias-Pulido, Xin-Yan Lu, Charles P Harris, Hernan Vargas, Fang F Zhang, Gopeshwar Narayan, Achim Schneider, Mary Beth Terry, Vundavalli VVS Murty, Chromosomal amplifications, 3q gain and deletions of 2q33-q37 are the frequent genetic changes in cervical carcinoma BMC Cancer. ,vol. 4, pp. 5- 5 ,(2004) , 10.1186/1471-2407-4-5
Ralph M. Richart, Bruce A. Barron, A follow-up study of patients with cervical dysplasia American Journal of Obstetrics and Gynecology. ,vol. 105, pp. 386- 393 ,(1969) , 10.1016/0002-9378(69)90268-3
J Bourhis, M G Le, M Barrois, A Gerbaulet, D Jeannel, P Duvillard, V Le Doussal, D Chassagne, G Riou, Prognostic value of c-myc proto-oncogene overexpression in early invasive carcinoma of the cervix. Journal of Clinical Oncology. ,vol. 8, pp. 1789- 1796 ,(1990) , 10.1200/JCO.1990.8.11.1789
Yen-Ying Ma, Sung-Jen Wei, Yu-Chen Lin, Jia-Chyi Lung, Ting-Chang Chang, Jacqueline Whang-Peng, Jacqueline M Liu, Deng-Mei Yang, Wen K Yang, Chen-Yang Shen, PIK3CA as an oncogene in cervical cancer Oncogene. ,vol. 19, pp. 2739- 2744 ,(2000) , 10.1038/SJ.ONC.1203597
Natalie Meyer, Linda Z. Penn, Reflecting on 25 years with MYC Nature Reviews Cancer. ,vol. 8, pp. 976- 990 ,(2008) , 10.1038/NRC2231
Magnus von Knebel Doeberitz, Miriam Reuschenbach, Dietmar Schmidt, Christine Bergeron, Biomarkers for cervical cancer screening: the role of p16(INK4a) to highlight transforming HPV infections. Expert Review of Proteomics. ,vol. 9, pp. 149- 163 ,(2012) , 10.1586/EPR.12.13