Spatial Omics Imaging of Fresh-Frozen Tissue and Routine FFPE Histopathology of a Single Cancer Needle Core Biopsy: A Freezing Device and Multimodal Workflow.

Abstract

The complex molecular alterations that underlie cancer pathophysiology are studied in depth with omics methods using bulk tissue extracts. For spatially resolved tissue diagnostics using needle biopsy cores, however, histopathological analysis using stained FFPE tissue and the immunohistochemistry (IHC) of a few marker proteins is currently the main clinical focus. Today, spatial omics imaging using MSI or IRI is an emerging diagnostic technology for the identification and classification of various cancer types. However, to conserve tissue-specific metabolomic states, fast, reliable, and precise methods for the preparation of fresh-frozen (FF) tissue sections are crucial. Such methods are often incompatible with clinical practice, since spatial metabolomics and the routine histopathology of needle biopsies currently require two biopsies for FF and FFPE sampling, respectively. Therefore, we developed a device and corresponding laboratory and computational workflows for the multimodal spatial omics analysis of fresh-frozen, longitudinally sectioned needle biopsies to accompany standard FFPE histopathology of the same biopsy core. As a proof-of-concept, we analyzed surgical human liver cancer specimens using IRI and MSI with precise co-registration and, following FFPE processing, by sequential clinical pathology analysis of the same biopsy core. This workflow allowed for a spatial comparison between different spectral profiles and alterations in tissue histology, as well as a direct comparison for histological diagnosis without the need for an extra biopsy.

• Authors: Miriam F Rittel, Stefan Schmidt, Cleo-Aron Weis, Emrullah Birgin, Björn van Marwick, Matthias Rädle, Steffen J Diehl, Nuh N Rahbari, Alexander Marx, Carsten Hopf
• Journal: Cancers (Cancers (Basel)) Vol. 15 Issue 10 (May 10 2023) ISSN: 2072-6694 [Print] Switzerland
• PMID: 37345020 (Publication Type: Journal Article)