4.5 Article

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

Journal

MICROSCOPY AND MICROANALYSIS
Volume 27, Issue 4, Pages 878-888

Publisher

OXFORD UNIV PRESS
DOI: 10.1017/S1431927621000507

Keywords

buccal mucosa; chromatin packing; early detection; electron microscopy; field cancerization; upper aerodigestive tract cancer

Funding

  1. Dutch Cancer Society [2014-7074]
  2. ZonMw [40-43500-984121, 91111.006]
  3. Dutch Technology for Life Sciences (DTL) enabling technology grant
  4. National Institutes of Health [R01CA200064, R33CA225323, R01CA225002]

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The study found significant differences in chromatin packing density and organization between cancer patients and controls, suggesting potential novel strategies for cancer risk assessment and diagnosis.
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.

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