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C-reactive protein biomarker possible predictor of progressive dysplasia
Increased levels of CRP together with age, lung function and pack-years of smoking can predict progressive dysplasia.
C-reactive protein (CRP) may predict whether precancerous bronchial dysplasia will progress to invasive carcinoma.
Two biopsies taken from the bronchial dysplastic lesions of 65 patients at study inception and at six months showed that half of the participants developed progressive dysplastic lesions and had baseline CRP levels 64% higher than participants who did not develop progressive disease (P = .027).
“These clinical data suggest that CRP levels, in conjunction with other simple clinical data, may be helpful in predicting which subjects with sputum atypia and bronchial dysplastic lesions will and will not progress to more advanced stages of dysplasia,” said Stephen Lam, MD, of the Lung Tumor Group, British Columbia Cancer Agency at the University of British Columbia in Vancouver, Canada.
The study appeared in the American Journal of Respiratory and Critical Care Medicine.
Animal models support the hypothesis that squamous cell carcinoma progresses in a stepwise manner from precancerous lesions, and “develops along the pathway of squamous metaplasia, dysplasia (of various grades), carcinoma in situ and then to invasive carcinoma.” Modeled on this observation, Lam and colleagues examined the predictive power of bronchial inflammation biomarkers. Their reasoning: Untreated bronchial inflammation can lead to dysplastic lesions and further to invasive carcinoma.
Of the 65 study patients, 45 (75%) were men and 48 were active smokers, each with at least one dysplastic lesion greater than 1.2 mm. Men were a mean 57 years of age and, on average, had 52 pack-years of smoking (the number of packs smoked per day multiplied by the number of years smoking). Researchers biopsied dysplastic lesions at the beginning of the study and after six months. They measured CRP, lung function and two other inflammatory markers at baseline and again at six months.
Half of the participants developed progressive dysplastic lesions after six months, and those men all had elevated baseline levels of CRP that were 64% higher than the participants who did not have progressive disease, according to researchers.
This study found a significant relationship between baseline CRP levels and progression of dysplastic lesions of participants at risk for developing non–small-cell lung cancer. Fifty-seven of 65 study participants showed elevated baseline CRP levels. Although only one of eight participants (13%) with CRP levels less than 0.5 mg/L developed progressive disease, 31 of 57 participants (54%, P = .011) with CRP levels greater than 0.5 mg/L developed progressive disease. Levels of CRP only differed among individuals whose bronchial lesions did or did not progress. Thirty-two (49%) of the 57 study participants developed progressive dysplasia while 33 (50%) had stable or regressed lesions. Of patients displaying progressive disease, 17 (53%) had lesions present at baseline that had deteriorated and 15 (47%) developed new dysplastic lesions.
The odds of developing progressive disease were almost 10-fold higher in the group displaying increased CRP levels, demonstrating the correlation between increased CRP levels and progressive dysplasia. Knowing the baseline CRP with lung function, age and pack-years of smoking “may allow investigators to predict with a reasonable degree of confidence which subjects will experience progressive disease and which will not,” Lam said.
Other biomarkers implicated in the progression of smoking-induced carcinomas are interleukins 6 and 8 and monocyte chemo-attractant protein-1. None was directly associated with progression of dysplastic lesions.
“It is possible that these inflammatory cytokines may not be involved in the progression of airway dysplasia. … Regardless of the exact cause, these biomarkers are likely to be less useful than CRP in predicting disease progression,” said Lam. Further study is needed to determine CRP’s role in the development of lung cancer, as it is not specific only to bronchial inflammation. – by Lyndsey Russell
For more information:
- Sin DD, Man SF, McWilliams A, Lam S. Progression of airway dysplasia and C-reactive protein in smokers at high risk of lung cancer. Am J Respir Crit Care Med. 2006;173:535-539.