Analytical Cellular Pathology

Analytical Cellular Pathology / 2010 / Article

Open Access

Volume 32 |Article ID 306087 |

Nan Yang, Esther R. Nijhuis, Haukeline H. Volders, Jasper J. H. Eijsink, Ágnes Lendvai, Bo Zhang, Harry Hollema, Ed Schuuring, G. Bea A. Wisman, Ate G. J. van der Zeea, "Gene Promoter Methylation Patterns throughout the Process of Cervical Carcinogenesis", Analytical Cellular Pathology, vol. 32, Article ID 306087, 13 pages, 2010.

Gene Promoter Methylation Patterns throughout the Process of Cervical Carcinogenesis


Objectives: To determine methylation status of nine genes, previously described to be frequently methylated in cervical cancer, in squamous intraepithelial lesions (SIL).Methods: QMSP was performed in normal cervix, low-grade (L)SIL, high-grade (H)SIL, adenocarcinomas and squamous cell cervical cancers, and in corresponding cervical scrapings.Results: Only CCNA1 was never methylated in normal cervices and rarely in LSILs. All other genes showed methylation in normal cervices, with CALCA, SPARC and RAR-β2 at high levels. Methylation frequency of 6 genes (DAPK, APC, TFPI2, SPARC, CCNA1 and CADM1) increased with severity of the underlying cervical lesion. DAPK showed the highest increase in methylation frequency between LSIL and HSIL (10% vs. 40%, p < 0.05), while CCNA1 and TFPI2 were most prominently methylated in cervical cancers compared to HSILs (25% vs. 52%, p < 0.05, 30% vs. 58%, p < 0.05). CADM1 methylation in cervical cancers was related to depth of invasion (p < 0.05) and lymph vascular space involvement (p < 0.01), suggesting a role in invasive potential of cervical cancers. Methylation ratios in scrapings reflected methylation status of the underlying lesions (p < 0.05).Conclusion: Methylation of previously reported cervical cancer specific genes frequently occurs in normal epithelium. However, frequency of methylation increases during cervical carcinogenesis, with CCNA1 and DAPK as the best markers to distinguish normal/LSIL from HSIL/cancer lesions.

Copyright © 2010 Hindawi Publishing Corporation and the authors. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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