Endometrial cancer is a common gynecologic cancer. Noninvasive molecular biomarkers for triage of high-risk patients for invasive procedures are needed. Based on the success of cytological Pap smear screening, cervical scrapings are a good source of DNA for molecular testing. In addition to genetic lesions, DNA methylation is a promising biomarker. We assessed the usefulness of combining genetic and epigenetic biomarkers from cervical scrapings to detect endometrial carcinomas. We performed a retrospective case–control study of 96 consecutive cervical scrapings from patients with abnormal uterine bleeding who underwent surgery for diagnostic evaluation. Thirty and 16 cases were diagnosed with type I and type II endometrial cancers, respectively. The remaining non-cancer cases included normal endometrium (n = 12), benign uterine lesions (n = 20), and endometrial hyperplasia (n = 18). Quantitative methylation-specific PCR and mass spectrometry were used for DNA methylation and genetic mutation analysis. Logistic regression was used to evaluate the clinical performance of these candidate biomarkers. We tested the effectiveness of the methylation status of four genes (BHLHE22, CDO1, TBX5, and HAND2) in endometrial cancer detection. The area under the receiver operating characteristic curves ranged from 0.703 to 0.878, and panels of hypermethylated BHLHE22/CDO1/HAND2 (87.0% sensitivity and 86.0% specificity) and BHLHE22/CDO1/TBX5 (89.1% sensitivity and 80.0% specificity) showed significant differences and could distinguish benign from malignant endometrial lesions. The sensitivity and specificity in endometrial cancer detection for BHLHE22/CDO1 were 84.8% and 88.0%, respectively. Both type I and II endometrial carcinomas could be detected using a BHLHE22/CDO1-based methylation profile, suggesting that they may have common epigenomes. Moreover, PTEN and TP53 mutations were found in 63.3% of type I and 93.6% of type II endometrial cancers. Unexpectedly, PTEN and TP53 mutations were commonly found in cervical scrapings of the normal endometrium (25% and 33.3%, respectively) and in cases with benign uterine lesions (10% and 50%, respectively). Finally, combinations of any one mutation of PTEN and TP53 mutations had a sensitivity of 91.3%, but a specificity of only 42.0%. Adding PTEN/TP53 mutation testing to BHLHE22/CDO1-based methylation testing did not improve the detection of endometrial cancer.

中文翻译：

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结合了基因突变和DNA甲基化基因作为生物标志物，可从宫颈刮屑中检测出子宫内膜癌。

子宫内膜癌是常见的妇科癌。需要用于对高风险患者进行侵入性分类的非侵入性分子生物标记物。基于细胞学巴氏涂片检查成功的基础，宫颈刮片是分子检测DNA的良好来源。除遗传损伤外，DNA甲基化也是有前途的生物标志物。我们评估了将宫颈刮片的遗传和后生生物标志物结合起来检测子宫内膜癌的有用性。我们进行了一项回顾性病例对照研究，对来自子宫异常出血患者的96例连续宫颈刮s患者进行了手术以进行诊断评估。分别诊断出I型和II型子宫内膜癌30例和16例。其余非癌病例包括子宫内膜正常（n = 12），子宫良性病变（n = 20），和子宫内膜增生（n = 18）。定量甲基化特异性PCR和质谱用于DNA甲基化和遗传突变分析。Logistic回归用于评估这些候选生物标志物的临床表现。我们测试了子宫内膜癌检测中四个基因（BHLHE22，CDO1，TBX5和HAND2）的甲基化状态的有效性。接收器工作特性曲线下的面积范围为0.703至0.878，高甲基化的BHLHE22 / CDO1 / HAND2（灵敏度为87.0％和86.0％）和BHLHE22 / CDO1 / TBX5（灵敏度为89.1％和80.0％）的面板显示出显着差异。可以区分良性和恶性子宫内膜病变。BHLHE22 / CDO1在子宫内膜癌检测中的敏感性和特异性分别为84.8％和88.0％。使用基于BHLHE22 / CDO1的甲基化谱图可以检测到I型和II型子宫内膜癌，这表明它们可能具有共同的表观基因组。此外，在I型子宫内膜癌的63.3％和II型子宫内膜癌的93.6％中发现了PTEN和TP53突变。出乎意料的是，PTEN和TP53突变通常在正常子宫内膜的宫颈刮片（分别为25％和33.3％）和子宫良性病变的病例（分别为10％和50％）中发现。最后，任何一种PTEN和TP53突变的组合的敏感性为91.3％，但特异性仅为42.0％。在基于BHLHE22 / CDO1的甲基化测试中添加PTEN / TP53突变测试并不能改善子宫内膜癌的检测。提示他们可能有共同的表观基因组。此外，在I型子宫内膜癌的63.3％和II型子宫内膜癌的93.6％中发现了PTEN和TP53突变。出乎意料的是，PTEN和TP53突变通常在正常子宫内膜的宫颈刮片（分别为25％和33.3％）和子宫良性病变的病例（分别为10％和50％）中发现。最后，任何一种PTEN和TP53突变的组合的敏感性为91.3％，但特异性仅为42.0％。在基于BHLHE22 / CDO1的甲基化测试中添加PTEN / TP53突变测试不能改善子宫内膜癌的检测。提示他们可能有共同的表观基因组。此外，在I型子宫内膜癌的63.3％和II型子宫内膜癌的93.6％中发现了PTEN和TP53突变。出乎意料的是，PTEN和TP53突变通常在正常子宫内膜的宫颈刮片（分别为25％和33.3％）和子宫良性病变的病例（分别为10％和50％）中发现。最后，任何一种PTEN和TP53突变的组合的敏感性为91.3％，但特异性仅为42.0％。在基于BHLHE22 / CDO1的甲基化测试中添加PTEN / TP53突变测试并不能改善子宫内膜癌的检测。）和子宫良性病变（分别为10％和50％）。最后，任何一种PTEN和TP53突变的组合的敏感性为91.3％，但特异性仅为42.0％。在基于BHLHE22 / CDO1的甲基化测试中添加PTEN / TP53突变测试并不能改善子宫内膜癌的检测。）和子宫良性病变（分别为10％和50％）。最后，任何一种PTEN和TP53突变的组合的敏感性为91.3％，但特异性仅为42.0％。在基于BHLHE22 / CDO1的甲基化测试中添加PTEN / TP53突变测试并不能改善子宫内膜癌的检测。