Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kita-gun, Japan.
Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita-gun, Japan.
J Hepatobiliary Pancreat Sci. 2023 Jun;30(6):802-814. doi: 10.1002/jhbp.1286. Epub 2022 Dec 20.
KRAS, P16, TP53, and SMAD4/DPC4 mutations are common in pancreatic ductal adenocarcinoma (PDAC). The study aimed to evaluate the association between gene mutations in pre-treatment endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) samples and clinical outcomes of patients with PDAC.
There were 43 patients with resectable (R) PDAC and 41 patients with borderline resectable (BR) PDAC. CDKN2A/p16, TP53, and SMAD4/DPC4 were evaluated through immunohistochemistry (IHC) of pretreatment EUS-FNA (n = 84) and resected specimens (n = 71). All patients received neoadjuvant therapy.
IHC of EUS-FNA specimens revealed p16 loss in 61 (73%), abnormal p53 in 61 (73%), and Smad4 loss in 38 (45%) patients. Abnormal p53 was associated with a lower resection rate (p = .017). Abnormal p53 and Smad4 loss were associated with recurrence within 6 months post-pancreatectomy (p = .03, p = .03, respectively). Univariate Cox regression analysis was conducted to reveal that abnormal p53 (p = .07), p16 loss and abnormal p53 (p = .04), and Smad4 and p16 loss (p = .03) were associated with poor prognosis.
Pre-treatment abnormal labeling of p53 in EUS-FNA specimen was associated with a lower resection rate and an early recurrence in R or BR PDAC cases.
KRAS、P16、TP53 和 SMAD4/DPC4 突变在胰腺导管腺癌(PDAC)中较为常见。本研究旨在评估 PDAC 患者术前内镜超声引导下细针抽吸(EUS-FNA)样本中基因突变与临床结局之间的关系。
共有 43 例可切除(R)PDAC 患者和 41 例交界可切除(BR)PDAC 患者。通过术前 EUS-FNA(n=84)和切除标本(n=71)的免疫组织化学(IHC)评估 CDKN2A/p16、TP53 和 SMAD4/DPC4。所有患者均接受新辅助治疗。
EUS-FNA 标本的 IHC 显示 61 例(73%)患者存在 p16 缺失、61 例(73%)患者存在异常 p53 和 38 例(45%)患者存在 Smad4 缺失。异常 p53 与较低的切除率相关(p=0.017)。异常 p53 和 Smad4 缺失与胰切除术后 6 个月内复发相关(p=0.03,p=0.03)。单因素 Cox 回归分析显示,异常 p53(p=0.07)、p16 缺失和异常 p53(p=0.04)以及 Smad4 和 p16 缺失(p=0.03)与预后不良相关。
EUS-FNA 标本中异常 p53 的术前标记与 R 或 BR PDAC 患者的较低切除率和早期复发相关。