BioWorld International Correspondent

LONDON - A new and simple test for esophageal cancer could be in general use within five years, allowing much earlier treatment and improving the outlook for patients. An initial evaluation has shown that it may allow accurate detection of the cancer long before any symptoms become apparent.

The test, which is easily automated, relies on finding a protein that is present only in cells with the potential to divide. It has been developed by the charity Cancer Research UK, which holds the patent on it. The commercial arm of the organization, Cancer Research Technology Ltd., is looking for commercial partners to help it develop the test further.

Kai Stoeber, lecturer at the Wolfson Institute for Biomedical Research at University College London, told BioWorld International: "Our results show that we can detect esophageal cancer with the same accuracy in fluid from the food pipe as we have already reported for bladder and prostate cancer using urine samples. This test is turning out to be applicable to a whole range of cancers in epithelial-lined organ systems. The implications for people with esophageal cancer are particularly important because until now there has been no test to diagnose this disease at an early stage before symptoms develop."

Stoeber, together with colleagues throughout the UK, reported an evaluation of the test in a paper in the British Journal of Cancer, titled "Diagnosis of oesophageal cancer by detection of minichromosome maintenance 5 protein in gastric aspirates."

Esophageal cancer is the ninth most common cancer in the UK, with more than 7,000 new cases and the same number of deaths each year. Its incidence has risen by 27 percent in the past 15 years. Those most at risk are people who smoke and/or drink heavily, who have a precancerous condition of the esophagus, or those who have been exposed to certain industrial pollutants.

Five-year survival following esophageal cancer in the UK currently is around 8 percent. One reason is that symptoms - which include difficulty in swallowing, pain while swallowing, weight loss, acid indigestion, regurgitation or vomiting, and hoarseness or chronic cough - often do not appear until the disease is at an advanced stage. In addition, many of those symptoms can be caused by other conditions, and it is difficult for the physician to know which patients need further investigation.

Patients who are referred to a specialist undergo endoscopy to allow a visual examination of the esophagus and, perhaps, a biopsy. The procedure is expensive, can be unpleasant and requires sedation.

The new test, which would be much less invasive, raises the prospect of being able to diagnose esophageal cancer at a stage when it may be cured. Early diagnosis, coupled with subsequent treatment by surgery and chemotherapy, can improve five-year survival rates to more than 80 percent.

The test detects levels of a protein, called MCM5, which is found only in cells that have the potential to divide. Such cells are not normally exposed on the surface epithelium of an organ - unless a tumor is present.

MCM5 is a member of the minichromosome maintenance proteins, which facilitate unwinding of the two parental DNA strands prior to DNA replication.

Since realizing the potential significance of MCM5, the team has developed an immunofluorometric test to detect it. Promising results already have been reported for its use in diagnosing cancer of the bladder and cancer of the prostate using urine samples, and a large trial involving 3,000 patients is under way for that application.

In the British Journal of Cancer, Stoeber and his colleagues report using the test on samples from 40 patients, half of whom had esophageal cancer, and half who did not. The test was able to identify cases of disease, distinguishing between patients with and without that type of cancer, with 85 percent accuracy.

A large-scale trial is planned, involving several thousand patients.

"We are now working toward making the collection of fluid samples from the esophagus as comfortable for the patient as possible," Stoeber said. "Instead of using an endoscope, we may look at using a nasogastric tube, a procedure which can be carried out at the local doctor's [office], without anesthetic."

Stoeber and his colleagues hope initially to examine the use of the test in the screening of high-risk groups.

No Comments