胰腺导管内乳头状黏液性肿瘤分子特征的临床意义

N. Peters, J. Kunstman
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引用次数: 4

摘要

导管内乳头状黏液性肿瘤(IPMN)是一种由胰腺导管引起的恶性前期、产生粘蛋白的上皮病变。观察报告将IPMN的行为定义为从无痛、无症状的病变到有时退化为胰腺癌的发育不良。IPMN管理的目标是降低高危囊肿的手术风险,并观察其余囊肿。区分高风险和低风险IPMN疾病仍然依赖于影像学和临床囊肿特征。在此,我们回顾了公认的IPMN分类,包括最常见的组织学亚型、其临床特征和目前公认的高危表型。然后,我们深入研究了IPMN的已知分子景观,这在很大程度上源于切除后的分析。这包括IPMN特有的基因变体,主要是GNAS和RNF43,但也检查了IPMN和传统胰腺癌之间的重叠。在临床环境中利用分子标记依赖于内镜下获得的囊肿液,并假设它准确地代表了囊性上皮的分子特征。我们综合了IPMN囊肿液突变分析的现有数据,并考虑了目前商业上可用的囊肿液分子分析试剂盒的优势和适当作用。我们的结论是,对切除的IPMN组织进行仔细解读的分子分析揭示了对其生物学和自然史的深入了解,而囊肿液分析则为指导治疗决策提供了预测和数据。然而,知识差距仍然存在,特别是在表征IPMN分子异质性、进展时间以及将囊肿液基因型数据与监测策略相关联方面。因此,在实现IPMN管理的真正分子指导之前,还需要大量的额外研究。Peters等人《癌症转移治疗杂志2021》第2页;7:31https://dx.doi.org/10.20517/2394-4722.2021.6718
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Clinical implications of the molecular characterization of intraductal papillary mucinous neoplasms of the pancreas
Intraductal papillary mucinous neoplasm (IPMN) is a pre-malignant, mucin-producing epithelial lesion arising from pancreatic ducts. Observational reports define IPMN behavior as ranging from indolent, asymptomatic lesions to dysplasia that sometimes degenerate into pancreatic adenocarcinoma. The goal of IPMN management is riskreducing surgery for high-risk cysts and observation of the remainder. Discriminating highfrom low-risk IPMN disease still relies on imaging and clinical cyst characteristics. Here, we review the accepted classification of IPMN including the most common histological subtypes, their clinical features, and currently-accepted high-risk phenotypes. We then deeply examine the known molecular landscape of IPMN, which has largely been derived from post-resection analysis. This includes those gene variants unique to IPMN, chiefly GNAS and RNF43, but also examines the overlap between IPMN and conventional pancreatic adenocarcinoma. Utilizing molecular markers in the clinical setting relies on endoscopically-obtained cyst fluid and presumes that it accurately represents the molecular characteristics of the cystic epithelium. We synthesize existing data on mutational analysis from IPMN cyst fluid and consider the benefits and proper role of current commercially-available cyst fluid molecular analysis kits. We conclude that carefully interpreted molecular analysis of resected IPMN tissue reveals insights into its biology and natural history while cyst fluid analysis offers prognostication and data to guide treatment decisions. However, knowledge gaps remain, especially in characterizing IPMN molecular heterogeneity, time to progression, and correlating cyst fluid genotype data with surveillance strategies. As such, substantial additional research is required before the promise of true molecular guidance of IPMN management can be realized. Page 2 of Peters et al. J Cancer Metastasis Treat 2021;7:31 https://dx.doi.org/10.20517/2394-4722.2021.67 18
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