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

Oisín Bugter, Yue Li, Anouk H.G. Wolters, Vasundhara Agrawal, Amil Dravid, Andrew Chang, Jose Hardillo, Ben N.G. Giepmans, Robert J. Baatenburg De Jong, Arjen Amelink, Vadim Backman, Dominic J. Robinson*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)878-888
Number of pages11
JournalMicroscopy and Microanalysis
Issue number4
Early online date1 Aug 2021
Publication statusPublished - Aug 2021

Bibliographical note

Funding Information:
The Dutch Cancer Society (2014-7074), ZonMw (40-43500-98-4121 and 91111.006) [a Dutch Technology for Life Sciences (DTL) enabling technology grant], and the National Institutes of Health (R01CA200064, R33CA225323, and R01CA225002) partly funded this study. They had no role in the study conception, design, data collection, analysis, data interpretation, or writing of the manuscript. The corresponding author had full access to all data and final responsibility for the decision to submit for publication.

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

Copyright 2021 Elsevier B.V., All rights reserved.


  • chromatin packing
  • early detection
  • electron microscopy
  • field cancerization
  • Key words buccal mucosa
  • upper aerodigestive tract cancer


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