Genetic expression, bronchoscopy increased lung cancer diagnostic sensitivity

The genetic signature identified 80% of 60 patients who developed lung cancer. Bronchoscopy diagnosed only 53% of those patients.

Issue: May 1, 2006

By adding a gene expression assay to flexible bronchoscopy, physicians may one day increase the sensitivity of diagnosing lung cancer in current or former smokers who are at risk for the disease, according to a presentation at the 97th Annual Meeting of the American Association for Cancer Research (AACR).

“The work that we are presenting here at AACR involves our attempts to develop an early diagnostic test for lung cancer in smokers who have suspicions of disease,” said Avrum Spira, MD, MSc, assistant professor of medicine and assistant professor of pathology and laboratory medicine, Boston University School of Medicine. “Pulmonary doctors are increasingly faced with the problem of smokers who are referred to our clinic – either current or former smokers – who have clinical suspicion of lung cancer.”

Unfortunately, Spira added, using bronchoscopy to find a lesion based on an abnormality seen in a chest x-ray or CT scan “has a low sensitivity for detection of lung cancer, especially at its earliest stage.”

Researchers took epithelial cells from the large airways of smokers during routine bronchoscopy and ran them through the Affymetrix HG-U133A microarray to develop an RNA expression signature. This genetic signature identified three times as many early-stage cancers as did conventional bronchoscopy, according to an AACR release.

“What we were able to do was develop a signature or group of genes that could accurately distinguish smokers who had lung cancer from smokers who did not have disease,” said Spira, who is also adjunct assistant professor of bioinformatics, Boston University College of Engineering, and director of bioinformatics and systems biology program at the pulmonary center at the university.

In this multicenter study, Spira and colleagues examined specimens collected from 152 smokers with a suspicion of lung cancer during a scheduled bronchoscopy. Patients were followed until they received a diagnosis, either benign disease or lung cancer.

The microarray complemented the clinical bronchoscopy results to identify 95% of patients with early- or late-stage lung cancers. By itself, the genetic signature identified 80% of 60 patients who developed lung cancer. Bronchoscopy diagnosed only 53% of those patients.

“By adding this gene expression test to the routine bronchoscopic study, we were able to increase the sensitivity and specificity of the procedure for detecting lung cancer. Combining the routine studies with our gene expression signature, we saw a 95% sensitivity of detection for lung cancer,” Spira said at a press conference during the meeting. “We increased the sensitivity for detection of stage I lung cancer from below 50% to above 90%, so we are very excited that this novel diagnostic test can be added on to an existing procedure and help detect lung cancer at its earliest stages in a population of individuals at risk for this disease.”

About 300,000 bronchoscopies are performed each year in the United States, according to the AACR. Bronchoscopy’s sensitivity for lung cancer ranges from 30% to 70%, depending on cancer stage. Where bronchoscopy is weakest, the genetic profiling is strongest, he said.

“The genetic signature from the airway epithelial cells does really well at the stage of disease that bronchoscopy is doing a poor job,” he said in a release. “Those are the early tumors, and if you make the diagnosis at that stage, you are more likely to have a cure with surgery and treatment than if you wait three months and the cancer has a chance to spread.”

The five-year survival rate for people diagnosed with stage IV lung cancer is less than 5%, Spira noted. Stage III survival averages less than 20% after five years. But with early detection of stage I disease, the five-year survival exceeds 60%, according to Spira.

“The difference is considerable,” he added. “Adding gene expression profiling of normal epithelial cells in the large airway to the bronchoscopy procedure enables clinicians to make earlier, more complete diagnosis and improves the opportunity for successfully treating more lung cancer patients.” – by Marie Rosenthal

For more information:

Spira A, Beane J, Shah V, et al. Airway gene expression: a novel diagnostic test for lung cancer in smokers. Abstract 2420. Presented at: 97th Annual Meeting of the American Association for Cancer Research; April 1-5, 2006; Washington.