LOS ANGELES — A combination of three biomarkers may reliably predict which patients with Barrett's esophagus will progress to esophageal adenocarcinoma, Dr. Patricia L. Blount reported at the annual meeting of the American Association for Cancer Research.
In a study involving 243 patients with Barrett's esophagus, 79.1% of patients who had all three genetic abnormalities on baseline endoscopic biopsy progressed to esophageal adenocarcinoma within 6 years. Conversely, among patients who had none of the abnormalities, there was not a single progression to cancer in almost 8 years. Progression rates for patients with one and two abnormalities were 5.7% and 28.4%, respectively, at 6 years.
Compared with patients with no abnormalities, patients with any two of the abnormalities were 9 times more likely to progress to esophageal adenocarcinoma, and those with all three of the abnormalities were 39 times more likely to progress during an average follow-up of 71 months; these differences were statistically significant. Patients with one abnormality were 1.8 times more likely to progress than those with no abnormalities, but this was not a significant difference.
In general, only about 10% of patients with Barrett's esophagus progress to esophageal adenocarcinoma, noted Dr. Blount, of the Fred Hutchinson Cancer Research Center, Seattle. Even frequent endoscopic surveillance can miss the small, focal lesions signaling progression to cancer. Thus, a reliable method of predicting progression could have far-reaching clinical effects. The investigators are working to translate this research into a practical test that does not require the facilities of a research laboratory, he said.
The investigators focused on DNA aneuploidy and tetraploidy and on alterations in the genes for the tumor-suppressor proteins TP53 and CDKN2A accompanied by a loss of heterozygosity (LOH) for those genes. Patients who had either aneuploidy or tetraploidy, 17p LOH (loss of heterozygosity on the short arm of chromosome 17), or 9p LOH (similarly, on chromosome 9) were more likely to progress to cancer.
As in other studies, the results of this study suggested that the use of NSAIDs may be protective against progression to esophageal adenocarcinoma.
The study was funded by the National Institutes of Health. Dr. Blount said that she had no conflicts of interest to disclose regarding the study.