‘Pill on a String’ Could Help Spot Early Signs of Esophageal Cancer
The Cytosponge, opened. Photo credit: University of Cambridge
Key Points
- Variations in mutations across the esophagus mean that standard biopsies may miss cells with important mutations. A sample was more likely to pick up key mutations if taken using the Cytosponge.
- Even in areas of Barrett’s esophagus without cancer, the researchers found a large number of mutations in their tissue—on average, 12,000 per person (compared to an average of 18,000 mutations within the cancer).
- More research into specifically which biomarkers and mutations mutations contribute to esophageal cancer is needed.
A “pill on a string” developed by researchers at the University of Cambridge could help doctors detect esophageal cancer at an early stage, helping them overcome the problem of wide variation between biopsies, suggests research published by Ross-Innes et al in Nature Genetics.
The Cytosponge
The Cytosponge sits within a pill which, when swallowed, dissolves to reveal a sponge that scrapes off cells when withdrawn up the gullet. It allows doctors to collect cells from all along the gullet, whereas standard biopsies take individual point samples.
Esophageal cancer is often preceded by Barrett’s esophagus, a condition in which cells within the lining of the esophagus begin to change shape and can grow abnormally. The cellular changes are caused by acid and bile reflux. Between one and five people in every 100 with Barrett’s esophagus go on to develop esophageal cancer in their lifetime.
At present, Barrett’s esophagus and esophageal cancer are diagnosed using biopsies, which look for signs of dysplasia. This is a subjective process, requiring a trained scientist to identify abnormalities. Understanding how esophageal cancer develops and the genetic mutations involved could help doctors catch the disease earlier, offering better treatment options for the patient.
An alternative way of spotting very early signs of esophageal cancer would be to look for important genetic changes. However, researchers from the University of Cambridge have shown that variations in mutations across the esophagus mean that standard biopsies may miss cells with important mutations. A sample was more likely to pick up key mutations if taken using the Cytosponge, developed by Rebecca Fitzgerald, MD, at the Medical Research Council Cancer Research Unit at the University of Cambridge.
“The trouble with Barrett’s esophagus is that it looks bland, and might span over 10 centimeters,” explained Dr. Fitzgerald. “We created a map of mutations in a patient with the condition and found that within this stretch, there is a great deal of variation amongst cells. Some might carry an important mutation, but many will not. If you're taking a biopsy, this relies on you hitting the right spot. Using the Cytosponge appears to remove some of this game of chance.”
Researchers also add that the Cytosponge is a cheaper tool than the standard esophageal biopsy, often performed during an endoscopy; patients are also more likely to agree to swallow the Cytosponge for screening as opposed to undergoing a larger procedure.
Study Details
Dr. Fitzgerald and colleagues conducted whole-genome sequencing to analyze paired Barrett’s esophagus and esophageal cancer samples taken at one point in time from 23 patients, as well as 73 samples taken over a 3-year period from one patient with Barrett’s esophagus.
The researchers found patterns of mutations in the genome that provided a “fingerprint” of the causes of the cancer. Similar work has been done previously in lung cancer, where it was shown that cigarettes leave such fingerprints in an individual's DNA. The Cambridge team found fingerprints that they believe are likely due to the damage caused to the lining of the esophagus by stomach acid splashing onto its walls; the same fingerprints could be seen in both Barrett’s esophagus and esophageal cancer, suggesting that these changes occur very early in the process.
Even in areas of Barrett’s esophagus without cancer, the researchers found a large number of mutations in their tissue—on average, 12,000 per person (compared to an average of 18,000 mutations within the cancer). Many of these are likely to have been “bystanders”—ie, genetic mutations that occurred along the way but that were not actually implicated in cancer.
The researchers found that there appeared to be a tipping point, where a patient would go from having many individual mutations but no cancer, to a situation where large pieces of genetic information were being transferred not just between genes, but between chromosomes.
Coauthor Caryn Ross-Innes, PhD, added, “We know very little about how you go from precancer to cancer, and this is particularly the case in esophageal cancer. Barrett’s esophagus and the cancer share many mutations, but we are now a step closer to understanding which are the important mutations that tip the condition over into a potentially deadly form of cancer.”
To view a more in-depth video of how the Cytosponge works, click here.
Dr. Fitzgerald is the corresponding author of the Nature Genetics article.
This study was funded by the Medical Research Council and Cancer Research UK.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
