Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Department of Obstetrics and Gynecology, Università degli Studi Milano-Bicocca, San Gerardo Hospital, Monza, Italy.
JAMA Netw Open. 2020 Jul 1;3(7):e207566. doi: 10.1001/jamanetworkopen.2020.7566.
The low 5-year survival rate of women with high-grade serous epithelial ovarian cancer (HGS-EOC) is related to its late diagnosis; thus, improvement in diagnosis constitutes a crucial step to increase the curability of this disease.
To determine whether the presence of the clonal pathogenic TP53 variant detected in matched primary tumor biopsies can be identified in DNA purified from Papanicolaou test samples collected from women with HGS-EOC years before the diagnosis.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted among a single-center cohort of women with histologically confirmed diagnosis of HGS-EOC recruited at San Gerardo Hospital, Monza, Italy, from October 15, 2015, to January 4, 2019. Serial dilutions of DNA derived from tumor samples and DNA extracted from healthy women's Papanicolaou test samples were analyzed to define the sensitivity and specificity of droplet digital polymerase chain reaction assays designed to detect the TP53 variants identified in tumors. All available brush-based Papanicolaou test slides performed up to 6 years before diagnosis were investigated at the Mario Negri Institute, Milano, Italy. Data were analyzed from October 2018 to December 2019.
The presence of tumor pathogenic TP53 variants was assessed by the droplet digital polymerase chain reaction approach in DNA purified from Papanicolaou test samples obtained from the same patients before diagnosis during cervical cancer screenings.
Among 17 included patients (median [interquartile range] age at diagnosis, 60 [53-69] years), Papanicolaou tests withdrawn before diagnosis presented tumor-matched TP53 variants in 11 patients (64%). In 2 patients for whom longitudinal Papanicolaou tests were available, including 1 patient with Papanicolaou tests from 25 and 49 months before diagnosis and 1 patient with Papanicolaou tests from 27 and 68 months before diagnosis, the TP53 clonal variant was detected at all time points.
These findings suggest that noninvasive early molecular diagnosis of HGS-EOC is potentially achievable through detection of TP53 clonal variants in the DNA purified from Papanicolaou tests performed during cervical cancer screening.
高级别浆液性上皮性卵巢癌（HGS-EOC）女性的 5 年生存率较低，这与晚期诊断有关；因此，改善诊断是提高这种疾病治愈率的关键步骤。
确定在诊断前数年收集的 HGS-EOC 女性巴氏涂片检查样本中是否可以检测到在匹配的原发性肿瘤活检中发现的克隆致病性 TP53 变体。
设计、环境和参与者：这项队列研究是在意大利蒙扎圣杰尔达医院的一个单中心队列中进行的，该队列纳入了 2015 年 10 月 15 日至 2019 年 1 月 4 日期间经组织学证实诊断为 HGS-EOC 的女性。分析了来自肿瘤样本的 DNA 及其衍生的连续稀释液以及从健康女性巴氏涂片检查样本中提取的 DNA，以确定旨在检测肿瘤中鉴定出的 TP53 变体的数字液滴聚合酶链反应检测的灵敏度和特异性。意大利米兰马里奥·内格里研究所调查了在诊断前长达 6 年进行的所有可用巴氏涂片检查刷载玻片。数据于 2018 年 10 月至 2019 年 12 月进行分析。
通过数字液滴聚合酶链反应方法评估从巴氏涂片检查样本中纯化的 DNA 中是否存在肿瘤致病性 TP53 变体，这些样本是在宫颈癌筛查期间从同一患者获得的，且在诊断前。
在纳入的 17 名患者中（诊断时的中位[四分位间距]年龄，60[53-69]岁），11 名患者（64%）的巴氏涂片检查在诊断前就存在肿瘤匹配的 TP53 变体。对于 2 名有纵向巴氏涂片检查的患者，包括 1 名巴氏涂片检查在诊断前 25 个月和 49 个月，以及 1 名巴氏涂片检查在诊断前 27 个月和 68 个月，在所有时间点均检测到 TP53 克隆变体。
这些发现表明，通过在宫颈癌筛查期间进行的巴氏涂片检查中检测 TP53 克隆变体，HGS-EOC 的非侵入性早期分子诊断是有可能实现的。
