DNA甲基化和P53免疫组织化学作为外阴硬皮病的预后生物标志物

IF 7.1 1区 医学 Q1 PATHOLOGY
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引用次数: 0

摘要

外阴硬皮病(LS)是一种炎症性皮肤病,可发展为与人乳头瘤病毒(HPV)无关的外阴上皮内瘤变(HPVi VIN)和外阴鳞状细胞癌(VSCC)。虽然与 HPVi VIN 相比,LS 的癌症风险要低得多(分别为 5%和 50%),但其发病率却要高得多。因此,临床上需要识别癌症风险增加的 LS 患者。我们的目的是研究DNA甲基化和p53免疫组化(IHC)作为LS患者癌症进展的预后生物标志物的价值。研究人员选取了 236 例患者的外阴组织,包括 75 例 LS 和 68 例 HPVi VIN(有癌变和无癌变)、32 例 VSCC 和 61 例健康外阴对照组。对样本进行了 p53 IHC 检测,并对包含 ZNF582、SST 和 miR124-2 的三基因标记面板进行了 DNA 甲基化分析。评估甲基化水平和 p53 IHC 状态(突变型或野生型),并在所有疾病类别中进行比较。测定了比值比(ORs),以确定生物标志物是否与LS患者的癌症进展相关。HPVi VIN 和 VSCC 的甲基化水平最高,其次是 LS 和健康外阴对照组。在 LS 病例中,甲基化水平的异质性最大。事实上,在 70% 发展为 VSCC 的 LS 中,三标记物面板检测呈阳性,而在未发展为癌症的 LS 患者中,只有 17% 呈阳性(p=0.002)。此外,与未发展为VSCC的LS病例相比,在发展为VSCC的LS病例中更常观察到突变p53 IHC(分别为42%和3%,p=0.001)。多变量分析发现,突变 p53 状态是 LS 癌症发展的唯一独立风险因素(OR 34.0,95% CI:1.4 - 807.4)。总之,DNA甲基化检测和p53 IHC显示出作为预后生物标志物的强大潜力,可用于识别LS患者的癌症进展高风险。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
DNA Methylation and P53 Immunohistochemistry as Prognostic Biomarkers for Vulvar Lichen Sclerosus

Vulvar lichen sclerosus (LS) is an inflammatory dermatosis that can progress to human papillomavirus (HPV)-independent vulvar intraepithelial neoplasia (HPVi VIN) and vulvar squamous cell carcinoma (VSCC). Although LS has a much lower cancer risk compared with HPVi VIN (5% versus 50%, respectively), its incidence is significantly higher. Therefore, there is a clinical need to identify LS patients with an increased cancer risk. Our objective was to study the value of DNA methylation and p53 immunohistochemistry (IHC) as prognostic biomarkers for progression to cancer in patients with LS. Vulvar tissues from 236 patients were selected, including 75 LS and 68 HPVi VIN, both with and without cancer development, 32 VSCC, and 61 healthy vulvar controls. Samples were subjected to p53 IHC and DNA methylation analysis of a 3-gene marker panel containing ZNF582, SST, and miR124-2. Methylation levels and p53 IHC status (mutant or wild-type) were assessed and compared among all disease categories. Odds ratios were determined to identify whether the biomarkers were associated with progression to cancer in patients with LS. The highest methylation levels were found in HPVi VIN and VSCC, followed by LS and healthy vulvar controls. The largest heterogeneity in methylation levels was observed in LS cases. In fact, the 3-marker panel tested positive in 70% of LS, which progressed to VSCC versus only 17% of LS in patients without cancer development (P = .002). Also, mutant p53 IHC was observed more frequently in LS with progression to VSCC compared with nonprogressive LS cases (42% versus 3%, respectively, P = .001). Multivariable analysis identified a mutant p53 status as the only independent risk factor for cancer development in LS (odds ratio: 34.0, 95% CI: 1.4-807.4). In conclusion, DNA methylation testing and p53 IHC show strong potential as prognostic biomarkers for the identification of LS patients at high risk of progression to cancer.

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来源期刊
Modern Pathology
Modern Pathology 医学-病理学
CiteScore
14.30
自引率
2.70%
发文量
174
审稿时长
18 days
期刊介绍: Modern Pathology, an international journal under the ownership of The United States & Canadian Academy of Pathology (USCAP), serves as an authoritative platform for publishing top-tier clinical and translational research studies in pathology. Original manuscripts are the primary focus of Modern Pathology, complemented by impactful editorials, reviews, and practice guidelines covering all facets of precision diagnostics in human pathology. The journal's scope includes advancements in molecular diagnostics and genomic classifications of diseases, breakthroughs in immune-oncology, computational science, applied bioinformatics, and digital pathology.
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