Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
Scancell Limited, University of Nottingham Biodiscovery Institute, University Park, Nottingham, NG7 2RD, UK.
Mol Diagn Ther. 2023 Mar;27(2):261-273. doi: 10.1007/s40291-022-00635-w. Epub 2023 Jan 19.
Targeted molecular imaging may improve tumor cell identification during diagnosis and resection of pancreatic ductal adenocarcinoma (PDAC). Although many molecular imaging biomarkers are (over)expressed in PDAC, intertumoral heterogeneity of biomarker expression hampers universal tracer administration. Preoperative, patient-specific screening and selection of the most optimal biomarker could therefore improve tumor delineation.
This study evaluated whether fine-needle biopsy (FNB) specimens could be used to preoperatively predict biomarker expression in the corresponding primary PDAC specimen.
Expression of previously identified PDAC biomarkers αβ, CEACAM5, EGFR, mesothelin, Le, and sdi-Le on FNB and corresponding primary tumor (PT) specimens (n = 45) was evaluated using immunohistochemistry and quantified using a semi-automated image analysis workflow.
Biomarker expression on FNB and PT tissues showed high concordance (∆H-score ≤ 50), i.e. was present in 62% of cases for αβ, 61% for CEACAM5, 85% for EGFR, 69% for mesothelin, 76% for Le, and 79% for sdi-Le, indicating high concordance. Except for αβ, biomarker expression on FNB tissues was positively correlated with PT expression for all biomarkers. Subgroup analyses showed that neoadjuvant therapy (NAT) had no major and/or significant effect on concordance, expression difference and, except for mesothelin, correlation of biomarker expression between FNB and PT tissues.
This study demonstrated that biomarker expression in FNB tissues is predictive for PT expression, irrespective of the application of NAT. These findings thereby provide the foundation for the clinical application of an FNB-based biomarker-screening workflow, eventually facilitating a patient-specific approach of molecular imaging tracer administration in PDAC.
靶向分子成像可能会提高在诊断和切除胰腺导管腺癌（PDAC）时对肿瘤细胞的识别能力。尽管许多分子成像生物标志物在 PDAC 中过度表达，但生物标志物表达的肿瘤间异质性阻碍了通用示踪剂的应用。因此，术前对患者进行特定的筛选，并选择最合适的生物标志物，可以改善肿瘤的描绘。
本研究评估了细针活检（FNB）标本是否可用于预测相应的原发性 PDAC 标本中生物标志物的表达。
使用免疫组织化学法评估了之前确定的 PDAC 生物标志物 αβ、CEACAM5、EGFR、间皮素、Le 和 sdi-Le 在 FNB 和相应的原发性肿瘤（PT）标本（n=45）上的表达，并使用半自动化图像分析工作流程进行定量。
FNB 和 PT 组织上的生物标志物表达具有高度一致性（∆H-score ≤ 50），即αβ在 62%的病例中存在，CEACAM5 在 61%的病例中存在，EGFR 在 85%的病例中存在，间皮素在 69%的病例中存在，Le 在 76%的病例中存在，sdi-Le 在 79%的病例中存在，表明具有高度一致性。除αβ外，所有生物标志物在 FNB 组织上的表达与 PT 表达呈正相关。亚组分析表明，新辅助治疗（NAT）对 FNB 和 PT 组织之间生物标志物表达的一致性、表达差异以及相关性没有重大和/或显著影响，除间皮素外。
本研究表明，FNB 组织中的生物标志物表达可预测 PT 表达，而与是否应用 NAT 无关。这些发现为基于 FNB 的生物标志物筛选工作流程的临床应用提供了基础，最终促进了 PDAC 中分子成像示踪剂的个体化给药方法。
