Buchberg Julie, de Stricker Karin, Pfeiffer Per, Mortensen Michael Bau, Detlefsen Sönke
Department of Pathology, Odense University Hospital, Odense, Denmark.
Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
Endosc Ultrasound. 2024 May-Jun;13(3):154-164. doi: 10.1097/eus.0000000000000072. Epub 2024 Jul 3.
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers, with a 5-year survival rate of around 9%. Only 20% are candidates for surgery. Most unresectable patients undergo EUS-guided fine-needle biopsy (EUS-FNB) for diagnosis. Identification of targetable mutations using next-generation sequencing (NGS) is increasingly requested. Data on feasibility of EUS-FNB for NGS and knowledge regarding mutational profile of unresectable PDAC are scarce. We evaluated the "technical yield" of EUS-FNB for NGS in unresectable PDAC: relative fraction of diagnostic EUS-FNBs meeting technical criteria. We also investigated the "molecular yield": relative fraction of EUS-FNBs included in NGS containing sufficient DNA for detection of at least one mutation. Furthermore, we determined the relative frequency of cancer-associated mutations in unresectable PDAC.
Formalin-fixed and paraffin-embedded EUS-FNBs diagnostic of unresectable PDAC and fulfilling these criteria were included ( = 105): minimum 3-mm tissue, minimum of 2-mm tumor area, and minimum 20% relative tumor area. NGS was performed using Ion GeneStudio S5 Prime System and Oncomine™ Comprehensive Assay v.3 including 161 cancer-related genes.
Technical yield was 48% (105/219) and molecular yield was 98% (103/105). Most frequently mutated genes were (89.3%) and (69.9%), followed by (24.3%), (9.7%), (7.8%), (7.8%), and (6.8%).
EUS-FNB for NGS of unresectable PDAC is feasible. Our technical criteria for NGS, using leftovers in formalin-fixed and paraffin-embedded blocks after routine pathology diagnosis, were met by around half of EUS-FNBs. Almost all EUS-FNBs fulfilling the technical criteria yielded a successful NGS analysis.
胰腺导管腺癌（PDAC）是致死率最高的癌症之一，5年生存率约为9%。仅20%的患者适合手术。大多数无法切除的患者接受超声内镜引导下细针穿刺活检（EUS-FNB）以进行诊断。越来越需要使用下一代测序（NGS）来鉴定可靶向的突变。关于EUS-FNB用于NGS的可行性以及不可切除PDAC突变谱的相关知识较为匮乏。我们评估了不可切除PDAC中EUS-FNB用于NGS的“技术成功率”：符合技术标准的诊断性EUS-FNB的相对比例。我们还研究了“分子成功率”：NGS中包含的EUS-FNB的相对比例，这些EUS-FNB含有足够的DNA以检测至少一种突变。此外，我们确定了不可切除PDAC中癌症相关突变的相对频率。
纳入经福尔马林固定、石蜡包埋且诊断为不可切除PDAC并符合以下标准的EUS-FNB标本（n = 105）：组织最小3毫米、肿瘤面积最小2毫米、相对肿瘤面积最小20%。使用Ion GeneStudio S5 Prime系统和Oncomine™ Comprehensive Assay v.3进行NGS检测，该检测包括161个与癌症相关的基因。
技术成功率为48%（105/219），分子成功率为98%（103/105）。最常发生突变的基因是KRAS（89.3%）和TP53（69.9%），其次是CDKN2A（24.3%）、SMAD4（9.7%）、PIK3CA（7.8%）、NRAS（7.8%）和BRAF（6.8%）。
不可切除PDAC的EUS-FNB用于NGS是可行的。我们用于NGS的技术标准，即使用常规病理诊断后福尔马林固定、石蜡包埋块中的剩余组织，约一半的EUS-FNB符合该标准。几乎所有符合技术标准的EUS-FNB都成功进行了NGS分析。
