Ghabi Elie M, Habib Joseph R, Shoucair Sami, Javed Ammar A, Sham Jonathan, Burns William R, Cameron John L, Ali Syed Z, Shin Eun Ji, Arcidiacono Paolo Giorgio, Doglioni Claudio, Falconi Massimo, Yu Jun, Partelli Stefano, He Jin
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ann Surg Oncol. 2023 Nov;30(12):7720-7730. doi: 10.1245/s10434-023-13965-8. Epub 2023 Jul 24.
Pancreatic neuroendocrine tumors (PanNETs) exhibit heterogenous behavior, whereby some small tumors are aggressive with a propensity for metastasis. Detection of somatic mutations associated with aggressive biology may help with patient stratification and surgical decision-making in patients with well-differentiated PanNETs. Using next-generation sequencing (NGS), we investigated the feasibility of detecting somatic mutations in endoscopic ultrasound-guided, fine-needle aspiration (EUS-FNA) specimens and determining the mutational concordance between the EUS-FNA specimens and the primary tumors.
Thirty-eight patients with well-differentiated, nonfunctioning PanNETs were obtained from two tertiary referral centers. Patient demographic characteristics and tumor, clinicopathologic features were collected. Tissue from both the EUS-FNA specimen and the primary tumor was extracted from archival tissue blocks. NGS using a panel of ten genes was performed on both samples.
In our series, the median age was 61.1 years. Tumors were predominantly left-sided (60.5%) and unifocal (94.7%). The median tumor size was 2.2 cm. NGS detected somatic mutations in 29% of primary tumors and 36.8% of EUS-FNA specimens. In primary tumors, DAXX/ATRX mutations were predominantly detected (63.6%). In EUS-FNA specimens, MEN1 mutations were predominantly detected (64.3%). Among non-wild-type specimens, mutational concordance was achieved in 31.6% of cases. In 11 patients with a detectable mutation in the primary tumor, a mutation was detected in the EUS-FNA specimen in 45.5% of cases, with a mutational concordance of 54.5%.
NGS can detect somatic mutations in EUS-FNA specimens of well-differentiated PanNETs. Efforts to improve detection sensitivity and mutational concordance are required to overcome current technical limitations.
胰腺神经内分泌肿瘤（PanNETs）表现出异质性，一些小肿瘤具有侵袭性且有转移倾向。检测与侵袭性生物学相关的体细胞突变可能有助于对分化良好的PanNETs患者进行分层及手术决策。我们使用下一代测序（NGS）技术，研究了在内镜超声引导下细针穿刺（EUS-FNA）标本中检测体细胞突变以及确定EUS-FNA标本与原发肿瘤之间突变一致性的可行性。
从两个三级转诊中心选取了38例分化良好的无功能性PanNETs患者。收集患者的人口统计学特征以及肿瘤的临床病理特征。从存档组织块中提取EUS-FNA标本和原发肿瘤的组织。对两个样本均进行包含十个基因的NGS检测。
在我们的研究系列中，中位年龄为61.1岁。肿瘤主要位于左侧（60.5%）且为单灶性（94.7%）。中位肿瘤大小为2.2厘米。NGS在29%的原发肿瘤和36.8%的EUS-FNA标本中检测到体细胞突变。在原发肿瘤中，主要检测到DAXX/ATRX突变（63.6%）。在EUS-FNA标本中，主要检测到MEN1突变（64.3%）。在非野生型标本中，31.6%的病例实现了突变一致性。在11例原发肿瘤中可检测到突变的患者中，45.5%的病例在EUS-FNA标本中检测到突变，突变一致性为54.5%。
NGS可在分化良好的PanNETs的EUS-FNA标本中检测到体细胞突变。需要努力提高检测灵敏度和突变一致性以克服当前的技术限制。
