Buck Achim, Ly Alice, Balluff Benjamin, Sun Na, Gorzolka Karin, Feuchtinger Annette, Janssen Klaus-Peter, Kuppen Peter J K, van de Velde Cornelis J H, Weirich Gregor, Erlmeier Franziska, Langer Rupert, Aubele Michaela, Zitzelsberger Horst, Aichler Michaela, Walch Axel
Research Unit Analytical Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
Centre for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
J Pathol. 2015 Sep;237(1):123-32. doi: 10.1002/path.4560. Epub 2015 Jun 30.
We present the first analytical approach to demonstrate the in situ imaging of metabolites from formalin-fixed, paraffin-embedded (FFPE) human tissue samples. Using high-resolution matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometry imaging (MALDI-FT-ICR MSI), we conducted a proof-of-principle experiment comparing metabolite measurements from FFPE and fresh frozen tissue sections, and found an overlap of 72% amongst 1700 m/z species. In particular, we observed conservation of biomedically relevant information at the metabolite level in FFPE tissues. In biomedical applications, we analysed tissues from 350 different cancer patients and were able to discriminate between normal and tumour tissues, and different tumours from the same organ, and found an independent prognostic factor for patient survival. This study demonstrates the ability to measure metabolites in FFPE tissues using MALDI-FT-ICR MSI, which can then be assigned to histology and clinical parameters. Our approach is a major technical, histochemical, and clinicopathological advance that highlights the potential for investigating diseases in archived FFPE tissues.
我们展示了第一种分析方法，用于证明对福尔马林固定、石蜡包埋（FFPE）的人体组织样本中的代谢物进行原位成像。使用高分辨率基质辅助激光解吸/电离傅里叶变换离子回旋共振质谱成像（MALDI-FT-ICR MSI），我们进行了一项原理验证实验，比较了FFPE组织切片和新鲜冷冻组织切片中的代谢物测量结果，发现在1700 m/z的物质中有72%存在重叠。特别是，我们观察到FFPE组织在代谢物水平上保留了与生物医学相关的信息。在生物医学应用中，我们分析了来自350名不同癌症患者的组织，能够区分正常组织和肿瘤组织，以及同一器官中的不同肿瘤，并发现了一个患者生存的独立预后因素。这项研究证明了使用MALDI-FT-ICR MSI测量FFPE组织中代谢物的能力，然后可以将其与组织学和临床参数相关联。我们的方法是一项重大的技术、组织化学和临床病理学进展，突出了在存档的FFPE组织中研究疾病的潜力。
