Mapping of the three-dimensional lymphatic microvasculature in bladder tumours using light-sheet microscopy

Nobuyuki Tanaka, Dagmara Kaczynska, Shigeaki Kanatani, Cecilia Sahlgren, Przemysław Mitura, Andrzej Stepulak, Ayako Miyakawa, Peter Wiklund, Per Uhlén

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Abstract

Background: Cancers are heterogeneous and contain various types of irregular structures that can go undetected when examining them with standard two-dimensional microscopes. Studies of intricate networks of vasculature systems, e.g., the tumour lymphatic microvessels, benefit largely from three-dimensional imaging data analysis. Methods: The new DIPCO (Diagnosing Immunolabeled Paraffin-Embedded Cleared Organs) imaging platform uses three-dimensional light-sheet microscopy and whole-mount immunolabelling of cleared samples to study proteins and micro-anatomies deep inside of tumours. Results: Here, we uncovered the whole three-dimensional lymphatic microvasculature of formalin-fixed paraffin-embedded (FFPE) tumours from a cohort of 30 patients with bladder cancer. Our results revealed more heterogeneous spatial deviations in more advanced bladder tumours. We also showed that three-dimensional imaging could determine tumour stage and identify vascular or lymphatic system invasion with higher accuracy than standard two-dimensional histological diagnostic methods. There was no association between sample storage times and outcomes, demonstrating that the DIPCO pipeline could be successfully applied on old FFPE samples. Conclusions: Studying tumour samples with three-dimensional imaging could help us understand the pathological nature of cancers and provide essential information that might improve the accuracy of cancer staging.

Original languageEnglish
Pages (from-to)995-999
Number of pages5
JournalBritish Journal of Cancer
Volume118
Issue number7
DOIs
Publication statusPublished - 1 Apr 2018

Keywords

  • Carcinoma, Transitional Cell/diagnosis
  • Formaldehyde
  • Humans
  • Imaging, Three-Dimensional
  • Lymphatic Vessels/diagnostic imaging
  • Microscopy/methods
  • Neoplasm Staging
  • Paraffin Embedding
  • Tissue Preservation/methods
  • Urinary Bladder Neoplasms/diagnosis

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  • Cite this

    Tanaka, N., Kaczynska, D., Kanatani, S., Sahlgren, C., Mitura, P., Stepulak, A., Miyakawa, A., Wiklund, P., & Uhlén, P. (2018). Mapping of the three-dimensional lymphatic microvasculature in bladder tumours using light-sheet microscopy. British Journal of Cancer, 118(7), 995-999. https://doi.org/10.1038/s41416-018-0016-y