新辅助治疗对近红外荧光成像食管癌组织肿瘤靶点表达的影响

IF 3 4区医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Molecular Imaging and Biology Pub Date : 2024-11-19 DOI:10.1007/s11307-024-01962-6

Hidde A Galema, Lisanne K A Neijenhuis, Lorraine J Lauwerends, N Geeske Dekker-Ensink, Cornelis Verhoef, Alexander L Vahrmeijer, Shadhvi S Bhairosingh, Peter J K Kuppen, Stephan Rogalla, Jacobus Burggraaf, Sjoerd M Lagarde, Bas P L Wijnhoven, Merlijn Hutteman, Michail Doukas, Stijn Keereweer, Denise E Hilling

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引用次数: 0

摘要

目的：新辅助化放疗（nCRT）后获得临床完全反应（CR）的卵巢癌患者是积极监测策略的候选者。初始临床完全反应后的再生率为40%，这表明鉴定nCRT的真正完全反应仍具有挑战性。近红外肿瘤特异性荧光内窥镜成像可能有助于区分真正完全反应患者和残留疾病患者。本研究旨在寻找潜在的标记物，以实现食道癌的分子成像，并评估 nCRT 对标记物表达的影响：收集诊断性活组织切片（n = 41）（治疗前）和配对手术标本（n = 31）（治疗后）的食管癌组织切片。其中包括腺癌（29 例）和鳞癌（12 例）患者的组织切片。通过免疫组织化学方法评估肿瘤标记物 CEA、EpCAM、VEGF-α、表皮生长因子受体（EGFR）和 c-MET 在肿瘤中的表达情况，并与周围健康组织中这些标记物的表达情况进行比较。免疫染色总分（TIS，范围 0-12）由染色细胞的百分比和强度综合计算得出。将治疗前活检样本的 TIS 与治疗后手术样本的 TIS 进行比较，以评估新辅助治疗对标记物表达的影响：结果：腺癌中EpCAM的中位TIS为10，而健康粘膜中为0（p 结论：EpCAM和表皮生长因子受体（EGFR）在腺癌中的中位TIS为10，而在健康粘膜中为0：EpCAM和表皮生长因子受体似乎分别是食管腺癌和鳞癌肿瘤特异性近红外荧光成像的最合适靶点。新辅助治疗不会影响所有合适标记物的表达，这意味着诊断性活检可用于选择患者特异性靶点，通过分子成像进行反应评估。

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Effects of Neoadjuvant Therapy on Tumour Target Expression of Oesophageal Cancer Tissue for NIR Fluorescence Imaging.

Purpose: Oesophaegal cancer patients with a clinical complete response (CR) after neoadjuvant chemoradiotherapy (nCRT) are candidates for an active surveillance strategy. Regrowth rates of 40% after initial clinical CR indicate that identification of a true complete response to nCRT remains challenging. Near-infrared tumour-specific fluorescence endoscopic imaging might help to discriminate patients with a true complete response from patients with residual disease. This study aims to find potential markers to enable molecular imaging in oesophageal cancer and to assess the effect of nCRT on marker expression.

Procedures: Oesophageal cancer tissue slides of diagnostic biopsies (n = 41) (pre-treatment) and paired surgical specimens (n = 31) (post-treatment) were collected. Tissue slides of patients with adenocarcinoma (n = 29) and squamous cell carcinoma (n = 12)) were included. Immunohistochemistry was performed to assess expression of the tumour markers CEA, EpCAM, VEGF-α, EGFR, and c-MET in the tumour and compared to the expression of these markers in surrounding healthy tissue. A total immunostaining score (TIS, range 0-12), which combines the percentage and intensity of stained cells, was calculated. The TIS of pre-treated biopsies were compared with the TIS of the post-treatment surgical specimens to assess the effect of neoadjuvant therapy on the marker expression.

Results: The median TIS of EpCAM in adenocarcinomas was 10, vs. 0 in healthy mucosa (p < 0.001). The median TIS of EGFR in squamous cell carcinoma was 12, vs. 4 in healthy mucosa (p < 0.001). Neoadjuvant therapy did not affect the expression of the markers.

Conclusion: EpCAM and EGFR appear to be the most suitable targets for tumour-specific NIR fluorescence imaging of oesophageal adenocarcinoma and squamous cell carcinoma, respectively. Unaffected expression of all suitable markers by neoadjuvant therapy implies that the diagnostic biopsy can be used to select a patient-specific target for response evaluation by molecular imaging.

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来源期刊

Molecular Imaging and Biology 医学-核医学

CiteScore

6.90

自引率

3.20%

发文量

审稿时长

3 months

期刊介绍： Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.