Microarray Sensitive for Detecting Early Lung Ca

WASHINGTON—Bronchoscopy, which is routinely used when there is suspicion of lung cancer, has a sensitivity ranging from 30% to 70%. Now, a gene expression microarray added to bronchoscopy has dramatically increased that figure, detecting 95% of lung cancers in initial studies with a high-risk population. "In this study, we piggy-backed an additional study onto this routine bronchoscopic procedure," said Avrum Spira, MD, of Boston University Medical Center. Dr. Spira led the study and presented the results at the 97th Annual Meeting of the American Association for Cancer Research (abstract 2420).

To develop the assay, the researchers first obtained normal epithelial cells from brushings of the right mainstem bronchus in patients—current and former smokers—who were undergoing bronchoscopy because of clinical suspicion of lung cancer. They then extracted RNA from the cells and applied it to the Affymetrix HG-U133A microarray chip. Patients were followed until they had a final diagnosis of either lung cancer or a benign condition.

The researchers divided the RNA into a training set of 77 samples and an independent test set of 52 samples. In the training set, an algorithm identified 80 genes whose pattern of expression distinguished between patients who had lung cancer and those who did not. The predictive pattern was then assessed in the test set.

In that independent set, the gene array had a sensitivity of 80%, and a specificity of 84%. Across all patients in the study with stage I lung cancer, sensitivity rose to 90%, compared with 36% for bronchoscopy alone.

Combined With Bronchoscopy

When the microarray pattern was combined with the bronchoscopy results, 95% of patients with early- or late-stage lung cancers were identified. And when it was projected onto a previously published lung cancer microarray, it distinguished lung cancer tissue from normal lung tissue with 90% accuracy.

"We are now in the process of working on developing a custom microarray that could potentially be used as a clinical adjunct to bronchoscopy," Dr. Spira said. The findings also may provide leads to molecular targets and pathways in lung cancer. Dr. Spira said that experiments are now being considered, using lung epithelial cells in culture, in which specific genes from the microarray will be turned on and off to see how they change the behavior of the cells.