Reporter 455, 25 September 2000
A diagnostic approach developed at the University of Leeds, bringing molecular biology into the clinic, offers new hope of identifying for timely treatment a group of patients at high risk of developing a life-threatening cancer.
About one in a hundred people have Barrett’s oesophagus, a condition in which the normal lining of the oesophagus (or gullet) is replaced by cells with a distinctive, column-like appearance under the microscope. These people are 40 times more likely than the average to develop oesophageal cancer – a disease that has doubled in incidence in the last decade in the UK.
Jordanian postgraduate surgeon Kamal Bani-Hani and colleagues at the University’s School of Medicine discovered that biopsy specimens from patients with Barrett’s oesophagus (known as BE) show up an excess of a particular protein, cyclin D1, and this could help identify which of them are likely to develop this cancer.
The protein has a part to play in regulating cell division, and overexpression is thought to be one of the genetic alterations associated with oesophageal cancer, the researchers report in the Journal of the National Cancer Institute.
The incidence of oesophageal cancer is increasing rapidly in the United States and Western Europe. Only a small fraction of the total patients with BE will develop the cancer – but diagnosis is normally made at an advanced stage, when the outlook is bleak. Therefore, a method is needed to indicate which patients are at increased risk.
The authors worked with 307 patients with BE between 1984 and1996. When the patients entered the study, and at intervals thereafter, endoscopic examinations were made and biopsy specimens were taken from the region of BE. Tissue specimens were analysed by staining with a specific antibody for overexpression of the protein cyclin D1.
Twelve patients with BE developed cancer of the oesophagus and each was matched with up to six control patients with BE who did not develop cancer. Sixty-seven percent of those who developed cancer had shown up positive for cyclin D1 when they were first diagnosed with BE. By contrast, only 29 percent of the matched control patients had biopsies that were positive for cyclin D1.
Patients whose biopsy specimens stained positive for the protein were six to seven times more likely to develop oesophageal cancer than the other patients. In some individuals, cyclin D1 overexpression was observed more than 10 years before diagnosis of the tumour.
Thus, the researchers found that cyclin D1 overexpression could be a useful biomarker of risk for the development of cancer of the oesophagus among BE patients.
Kamal Bani-Hani, who researched at Leeds under Professor Chris Wild of the Molecular Epidemiology Unit and Leeds General Infirmary surgeon Iain Martin, is now teaching in the medical school at Jordan University of Science & Technology.
Prof Wild said his student’s findings would have useful resource implications for health services as well as helping in the clinical tracking of individual cases.
"Instead of being called in for tests at, say, two-year intervals, the higher-risk group could be monitored more frequently. Costs and discomfort could be reduced by avoiding unnecessary tests on low-risk patients, while the survival rates of the higher-risk people should be improved," he said.
"It’s quite exciting, too, as an example of collaboration between basic research and clinical practice at the University/NHS interface."
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