Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Surgery CCM|CVK, Charité, Universitätsmedizin Berlin, Germany; Graduate School of Life Sciences, Utrecht University, The Netherlands.
Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Pancreatology. 2023 Nov;23(7):868-877. doi: 10.1016/j.pan.2023.05.005. Epub 2023 May 15.
Mucinous pancreatic cysts harbor the potential to progress to highly lethal pancreatic ductal adenocarcinoma (PDAC). Since these precursor cysts require cancer surveillance or surgical resection, they need to be reliably distinguished from harmless pancreatic cysts. Current clinical and radiographic assessment is imperfect and the value of cyst fluid analysis for differential diagnosis is unclear. Therefore, we set out to investigate the value of cyst fluid biomarkers in distinguishing pancreatic cysts.
We performed a systematic review of the current literature to identify articles that evaluated the diagnostic performance of clinically relevant and promising candidate cyst fluid biomarkers, with a particular emphasis on DNA-based biomarkers. Meta-analysis was performed for biomarkers targeted at identifying cyst type and presence of high-grade dysplasia or PDAC.
Data from a total of 42 studies was analyzed. Mutations in KRAS and/or GNAS allowed identification of mucinous cysts with a sensitivity of 79% and specificity of 98%. This exceeded the performance of the traditional biomarker carcinoembryonic antigen (CEA; sensitivity 58%, specificity 87%). Mutations in VHL were specific for serous cystadenomas (SCAs; sensitivity 56%, specificity 99%) and help to exclude mucinous cysts. Mutations in CDKN2A, PIK3CA, SMAD4, and TP53 each had high specificities of 97%, 97%, 98%, and 95%, respectively, to identify high-grade dysplasia or PDAC in mucinous cysts.
Cyst fluid analysis can be a valuable tool in the characterization of pancreatic cysts, with relevant clinical implications. Our results support the use of DNA-based cyst fluid biomarkers in the multidisciplinary diagnostic work-up of pancreatic cysts.
黏液性胰腺囊肿有进展为高度致命的胰腺导管腺癌（PDAC）的潜力。由于这些前体囊肿需要癌症监测或手术切除，因此需要将其与无害的胰腺囊肿可靠地区分开来。目前的临床和影像学评估并不完善，囊液分析在鉴别诊断中的价值也不清楚。因此，我们着手研究囊液生物标志物在鉴别胰腺囊肿方面的价值。
我们对当前文献进行了系统回顾，以确定评估临床相关和有前途的候选囊液生物标志物诊断性能的文章，特别强调基于 DNA 的生物标志物。对用于识别囊肿类型以及存在高级别发育不良或 PDAC 的生物标志物进行了荟萃分析。
共分析了 42 项研究的数据。KRAS 和/或 GNAS 的突变可识别黏液性囊肿，其敏感性为 79%，特异性为 98%。这优于传统标志物癌胚抗原（CEA；敏感性 58%，特异性 87%）的性能。VHL 的突变特异性针对浆液性囊腺瘤（SCA；敏感性 56%，特异性 99%），有助于排除黏液性囊肿。CDKN2A、PIK3CA、SMAD4 和 TP53 的突变分别具有 97%、97%、98%和 95%的高特异性，可识别黏液性囊肿中的高级别发育不良或 PDAC。
囊液分析可以成为胰腺囊肿特征描述的一种有价值的工具，具有相关的临床意义。我们的研究结果支持在胰腺囊肿的多学科诊断工作中使用基于 DNA 的囊液生物标志物。
