Tuesday January 17 2012
A spray has been designed to detect the early signs of oesophageal cancer
“A throat spray has been developed to spot cancer of the oesophagus at an early stage,” according to the Daily Mail. The paper says that the test “offers hope” to the 8,000 Britons diagnosed with the cancer each year.
Contrary to what the media has suggested, scientists were not trying to develop a way to screen the general population routinely for cancer of the oesophagus (also known as our “food pipe”). Instead, doctors have looked at ways to check for abnormal cells in a very specific condition called Barrett’s oesophagus. People with Barrett’s oesophagus have abnormal cells along their oesophagus that have a a greater chance of becoming cancerous than normal cells.
In this study, scientists developed a fluorescent chemical that latched most strongly onto healthy cells and less strongly on abnormal cells that were becoming cancerous. This allowed them to identify potentially dangerous clumps of cells in the tissue taken from people with Barrett’s oesophagus.
This is early research and the detection technique has so far only been tested in sections of the oesophagus removed from four patients. It is also important to note that this technique is not being assessed as a way to screen the general population for oesophageal cancer, but to detect areas of tissue that are progressing in people who have a condition that predisposes them to this cancer.
The technique will need to be studied further to assess whether it would be feasible, effective and safe in clinical practice and whether it offers real advantages over existing techniques.
Where did the story come from?
The study was carried out by researchers from the Medical Research Council Cancer Cell Unit in Cambridge and from other research centres in the UK and US. The study was funded by various sources, including the GlaxoSmithKline pharmaceutical company, the Cambridge Experimental Medicine Centre, the National Institute for Health Research, Cancer Research UK, the US National Institutes of Health and the Department of Health’s NIHR Biomedical Research Centre. The study was published in the peer-reviewed journal Nature Medicine.
The Daily Mail’s coverage over-generalises the implications of this research, suggesting that it offers hope to all people diagnosed with oesophageal cancer. Its coverage also implies that this technique might be used in screening the general population for this cancer. However, the research is at a very early stage, and has so far only been tested on tissue from people who have the precancerous condition Barrett’s oesophagus.
What kind of research was this?
This was laboratory research investigating new ways to detect potentially cancerous cells in the throat and oesophagus (food pipe). It looked at a precancerous condition called Barrett’s oesophagus, in which people with chronic acid reflux develop abnormal growths of cells within the lower oesophagus. These cells are at greater risk of developing into a type of oesophageal cancer. Although these cells can potentially become cancerous, they are not routinely removed at this stage as such surgery would be invasive, and not all people with Barrett’s oesophagus develop oesophageal cancer.
For people with Barrett’s oesophagus who develop oesophageal cancer, the outlook would be better if any cancerous changes were detected early, before symptoms occurred. The methods used in this study are typical of early stage research aimed at developing ways to detect cancerous cells.
It is difficult to identify potentially cancerous tissue and to look at a large area of tissue using currently available methods, which rely on using microscopes. The researchers wanted to develop a technique that avoided these problems by developing a fluorescent marker that would either attach to cells that were becoming cancerous but not normal cells, or vice versa.
What did the research involve?
The researchers started by looking at one group of molecules called glycans, which are made up of long strings of sugar molecules joined together. They are found on the surface of cells and undergo changes in cancerous cells, including those of oesophageal cancer. The researchers assessed what changes occurred in the production and breakdown of glycans as the cells developed from Barrett’s oesophagus through to intermediate stages called “low grade dysplasia” and “high grade dysplasia”, and then to oesophageal cancer. They did this by using tissue samples at the different stages.
Glycans bind to protein molecules called lectins that are found in plants and animals. The researchers next looked at whether the changes in glyans affected how they could bind to different lectins. Once they found differences, they selected one specific lectin that showed the greatest difference between health and abnormal cells to study further. They then attempted to confirm their results for this lectin by fluorescently “tagging” it, allowing them to detect under a microscope how it bound to healthy and abnormal tissue. In this part of the experiment they used 80 tissue biopsies representing the different stages of Barrett’s oesophagus development.
Finally, the researchers then tested out their fluorescently tagged lectin in sections of oesophagus that had just been surgically removed from four patients who were known to have Barrett’s oesophagus. Three of them were known to have early cancerous lesions, and one to have more advanced lesions.
The researchers tried to test their system by mimicking the techniques that would be used in a standard examination of oesophagus. An endoscope (a long tube with a camera and lights in it) was placed in the section of oesophageal tube in the laboratory. This procedure would normally be carried out to look for cancerous-looking tissue in the oesophagus in a patient. The researchers used the endoscope to look at the oesophagus using normal (white) light and a fluorescent light (to see if there was any natural fluorescence before applying their fluorescently tagged lectin). They then sprayed the oesophagus with the fluorescently tagged lectin and looked at it again with the fluorescent light to see what patterns of fluorescence they could see. They compared the results from the fluorescence with what was seen when they looked at the tissue under the microscope.
What were the basic results?
The researchers found that changes in glycan production and breakdown occurred as Barrett’s oesophagus cells developed towards the cancerous stage. These changes could be used to identify tissue that was progressing towards cancer before it became cancerous.
The researchers found that the changes in glycans affected how they bound to four specific lectins that are found in types of fungi, snails and plants. They found that the greatest changes in binding were seen with one lectin that came from a fungus (Aspergillus) and one that came from wheatgerm. As wheatgerm is a normal part of the human diet, they chose this lectin for further study as it should not be harmful to humans.
The researchers then fluorescently tagged this wheatgerm lectin and added it to biopsied oesophageal tissue in the laboratory at different stages of development. They found that the closer the lectin was to being cancerous, the less it bound to the tissue. This meant that healthier tissue showed up as being more fluorescent than tissue that had progressed towards being cancerous. This is the opposite to their original goal, which was to create a system that would highlight cancerous cells but not healthy cells.
Finally, the researchers tested the fluorescently tagged lectin in sections of oesophagus immediately after removal from patients. They saw that in the patient with the most advanced lesions these lesions showed low levels of fluorescence, while areas of less advanced Barrett’s oesophagus or normal oesophageal tissue showed higher levels of fluorescence.
In two patients known to have less advanced lesions, lesions could not be seen in the oesophagus under the normal light. However, when placed under UV light the fluorescent lectin showed up areas of abnormal tissue that were progressing towards being cancerous.
Overall in these three patients, the abnormal, precancerous tissue showed on average five times less fluorescence than the surrounding normal tissue. The level of fluorescence of an area of tissue also corresponded with how abnormal the tissue looked under the microscope.
The final patient had their entire oesophagus removed, and no abnormalities were visible using the fluorescent lectin assessment outside of the body. This was also the case when the tissue was examined under the microscope. There was one area of high-grade dysplasia found under the microscope, but this was underneath the top layer of the oesophagus so would not have been detectable by the fluorescent lectin technique.
How did the researchers interpret the results?
The researchers concluded that lectins are relatively cheap, non-toxic molecules, which, when fluorescently labelled, could provide a viable way to screen for progression towards cancer in people with Barrett’s oesophagus. This could help identify areas to be biopsied or removed in the patient.
This small study has developed a fluorescently tagged molecule that can help identify areas of Barrett’s oesophagus that have progressed towards becoming cancerous. This is an early study with limitations, including the following:
- This was a small study, which only tested the technique in sections of oesophagus from four patients.
- The study only looked at oesophageal samples that had been removed from the body, although the researchers did try to replicate how the oesophagus would be examined in real life.
- The fluorescent molecule binds more strongly to normal tissue and less strongly to abnormal tissue. The researchers note that an ideal marker for cancerous tissue would usually work in the opposite way: binding to abnormal tissue but not normal tissue.
- This study was only in people who have a precancerous condition called Barrett’s oesophagus. It is not clear whether the technique would be useful in people who do not have this condition, particularly within a routine screening setting.
- The technique could only detect patches of dysplastic (abnormal) tissue on the surface of the oesophagus. This may mean that it misses some abnormal tissue that could become cancerous.
Although this technique shows some promise, further studies are needed to assess whether it would be feasible, effective and safe in clinical practice. This will include looking at oesophageal tissue in patients rather than in the lab, and comparing how well it performs against or alongside existing techniques.