| Autor: |
Voss, Féline O., Thuijs, Nikki B., Duin, Sylvia, Özer, Müjde, van Beurden, Marc, Berkhof, Johannes, Steenbergen, Renske D. M., Bleeker, Maaike C. G. |
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| Zdroj: |
International Journal of Cancer; Aug2023, Vol. 153 Issue 4, p783-791, 9p |
| Abstrakt: |
The precursor lesions of vulvar squamous cell carcinoma (VSCC) include human papillomavirus (HPV)‐associated and HPV‐independent squamous neoplasia with a varying cancer risk. Our study aimed to validate the accuracy of previously identified DNA methylation markers for detection of such high‐grade vulvar intraepithelial neoplasia (VIN). A large clinical series of 751 vulvar lesions, originally diagnosed as high‐grade VIN, were reassessed and categorized into HPV‐associated or HPV‐independent vulvar disease categories. Together with 113 healthy vulvar controls, all samples were tested for 12 methylation markers with quantitative multiplex methylation‐specific PCR (qMSP). Performance of individual markers and selection of an optimal marker panel for detection of high‐grade VIN was determined by logistic regression analysis. SST was the best‐performing individual marker (AUC 0.90), detecting 80% of high‐grade VIN cases, with excellent detection of HPV‐independent VIN (95%), known to have the highest cancer risk. Merely 2% of controls tested methylation positive for SST. Selection of a marker panel, including ZNF582, SST and miR124‐2, resulted in a comparably high accuracy for detection of high‐grade VIN (AUC 0.89). In conclusion, we clinically validated the accuracy of 12 DNA methylation markers for detection of high‐grade VIN. SST, as a sole marker or in a panel, provides an optimal diagnostic tool to distinguish high‐grade VIN in need of treatment, particularly HPV‐independent VIN, from low‐grade or reactive vulvar lesions. These findings warrant further prognostic validation of methylation biomarkers for cancer risk stratification of patients with VIN. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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