Inflammatory biomarker helps identify progressive precancerous lesions in the lung

C-reactive protein (CRP), a biomarker for inflammation in the blood, can help to identify individuals whose abnormal precancerous lesions will advance closer to invasive lung cancer.

The results appear in the first issue for March 2005 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Stephen Lam, M.D., F.R.C.P.C., of the Lung Tumour Group, British Columbia Cancer Agency at the University of British Columbia in Vancouver, Canada, and three associates measured CRP, lung function and other inflammatory markers in 65 individuals. All participants had at least one abnormal cell site in their lungs (bronchial dysplasia) greater than 1.2 millimeters in size, which was biopsied at the start of the study and re-examined 6 months later.

Of the study cohort, 49 individuals (75 percent) were men, with 48 classified as current smokers. On average, study participants were 57 years old and had 52 pack-years of smoking history.

“Lung cancer is a worldwide epidemic,” said Dr. Lam. “More than 300 million people die of this disease annually. In the United States alone, 170,000 new cases of lung cancer are reported each year. Most of these are non-small cell lung cancer and the overall prognosis once diagnosed is dismal. The only reasonable chance of cure is surgical resection for early stage tumors. However, most patients with early lung cancer are asymptomatic. Symptoms usually develop after the tumors become invasive or disseminated and curative resection is infeasible.”

Consequently, researchers have been working to find novel non-invasive or semi-invasive methods of identifying individuals who harbor progressive precancerous lesions. If detected early, these lesions might be treated with a chemopreventive agent to impede progress to invasive carcinoma.

In the study, the level of CRP only differed between individuals who either did or did not develop progression in their bronchial lesions.

“The odds of developing progressive disease were 9.6 fold higher in the group that had CRP greater than 0.5 mg per liter compared with the group less than this threshold,” said Dr. Lam.

There were 32 subjects whose bronchial lesions had progressed to a more abnormal state when biopsied after 6 months.

“These data are consistent with the prevailing hypothesis that squamous cell carcinoma arises from preinvasive lesions in stepwise fashion, which is called the sequential theory of cancer development,” said Dr. Lam. “This hypothesis is supported by animal experiments mimicking human carcinogenesis.”

The authors believe that these results will be helpful in designing future chemopreventive and early detection studies by identifying high-risk subjects for non-small cell lung cancer.