Immunology and Molecular Oncology Diagnostics Unit, Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, Italy.
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", 47014 Meldola, Italy.
Int J Mol Sci. 2024 Oct 15;25(20):11090. doi: 10.3390/ijms252011090.
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited survival. Curative opportunities are only available for patients with resectable cancer. Palliative chemotherapy is the current standard of care for unresectable tumors. Numerous efforts have been made to investigate new therapeutic strategies for PDAC. Immunotherapy has been found to be effective in treating tumors with high microsatellite instability (MSI-H), including PDAC. The ability of the Endoscopic Ultrasound Fine Needle Biopsy (EUS-FNB) to reliably collect tissue could enhance new personalized treatment by permitting genomic alterations analysis. The aim of this study was to investigate the feasibility of obtaining adequate DNA for molecular analysis from EUS-FNB formalin-fixed-paraffin-embedded (FFPE) specimens. For this purpose, FFPE-DNA obtained from 43 PDAC archival samples was evaluated to verify adequacy in terms of quantity and quality and was tested to evaluate MSI-H status by droplet digital PCR (ddPCR). All samples were suitable for ddPCR analysis. Unlike the 1-2% MSI-H frequency found with traditional techniques, ddPCR detected this phenotype in 16.28% of cases. This study suggests the ddPCR ability to identify MSI-H phenotype, with the possibility of improving the selection of patients who may benefit from immunotherapy and who would be excluded by performing traditional diagnostic methods.
胰腺导管腺癌 (PDAC) 是一种侵袭性很强的疾病，患者的生存时间有限。只有可切除癌症患者才有治愈机会。不可切除肿瘤的当前标准治疗方法是姑息性化疗。人们已经做出了许多努力来研究 PDAC 的新治疗策略。免疫疗法已被证明对高度微卫星不稳定 (MSI-H) 的肿瘤有效，包括 PDAC。内镜超声细针活检 (EUS-FNB) 可靠地采集组织的能力可以通过允许基因组改变分析来增强新的个性化治疗。本研究旨在探讨从 EUS-FNB 福尔马林固定石蜡包埋 (FFPE) 标本中获得足够用于分子分析的 DNA 的可行性。为此，评估了 43 个 PDAC 存档样本的 FFPE-DNA，以验证其在数量和质量方面的充分性，并通过液滴数字 PCR (ddPCR) 测试来评估 MSI-H 状态。所有样本均适合 ddPCR 分析。与传统技术发现的 1-2% MSI-H 频率不同，ddPCR 在 16.28%的病例中检测到这种表型。本研究表明 ddPCR 能够识别 MSI-H 表型，有可能通过进行传统诊断方法来改善选择可能受益于免疫疗法的患者，并排除可能受益于免疫疗法的患者。
