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Early Upper Aerodigestive Tract Cancer Detection Using Electron Microscopy to Reveal Chromatin Packing Alterations in Buccal Mucosa Cells

Published online by Cambridge University Press:  10 June 2021

Oisín Bugter
Affiliation:
Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, Postbus 2040, 3000CARotterdam, the Netherlands Center for Optical Diagnostics and Therapy, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, Postbus 2040, 3000CARotterdam, the Netherlands
Yue Li
Affiliation:
Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL60208, USA
Anouk H.G. Wolters
Affiliation:
Department of Biomedical Sciences of Cells and Systems, University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, 9713 AVGroningen, the Netherlands
Vasundhara Agrawal
Affiliation:
Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL60208, USA
Amil Dravid
Affiliation:
Department of Electrical Engineering and Computer Science, Northwestern University, 2145 Sheridan Road, Evanston, IL60208, USA
Andrew Chang
Affiliation:
Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL60208, USA
Jose Hardillo
Affiliation:
Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, Postbus 2040, 3000CARotterdam, the Netherlands
Ben N.G. Giepmans
Affiliation:
Department of Biomedical Sciences of Cells and Systems, University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, 9713 AVGroningen, the Netherlands
Robert J. Baatenburg de Jong
Affiliation:
Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, Postbus 2040, 3000CARotterdam, the Netherlands
Arjen Amelink
Affiliation:
Department of Optics, the Netherlands Organization for Applied Scientific Research (TNO), Stieltjesweg 1, 2628 CKDelft, the Netherlands Department of Physics and Astronomy, Vrije Universiteit Amsterdam, De Boelelaan 1081, 1081 HVAmsterdam, the Netherlands
Vadim Backman
Affiliation:
Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL60208, USA
Dominic J. Robinson*
Affiliation:
Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, Postbus 2040, 3000CARotterdam, the Netherlands Center for Optical Diagnostics and Therapy, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, Postbus 2040, 3000CARotterdam, the Netherlands
*
*Author for correspondence: Dominic J. Robinson, E-mail: d.robinson@erasmusmc.nl

Abstract

A profound characteristic of field cancerization is alterations in chromatin packing. This study aimed to quantify these alterations using electron microscopy image analysis of buccal mucosa cells of laryngeal, esophageal, and lung cancer patients. Analysis was done on normal-appearing mucosa, believed to be within the cancerization field, and not tumor itself. Large-scale electron microscopy (nanotomy) images were acquired of cancer patients and controls. Within the nuclei, the chromatin packing of euchromatin and heterochromatin was characterized. Furthermore, the chromatin organization was quantified through chromatin packing density scaling. A significant difference was found between the cancer and control groups in the chromatin packing density scaling parameter for length scales below the optical diffraction limit (200 nm) in both the euchromatin (p = 0.002) and the heterochromatin (p = 0.006). The chromatin packing scaling analysis also indicated that the chromatin organization of cancer patients deviated significantly from the control group. They might allow for novel strategies for cancer risk stratification and diagnosis with high sensitivity. This could aid clinicians in personalizing screening strategies for high-risk patients and follow-up strategies for treated cancer patients.

Type
Biological Applications
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press on behalf of the Microscopy Society of America

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Footnotes

The first two authors contributed equally to this work.

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Early Upper Aerodigestive Tract Cancer Detection Using Electron Microscopy to Reveal Chromatin Packing Alterations in Buccal Mucosa Cells
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