TY - JOUR
T1 - Long-term impact of smoking on lung epithelial proliferation in current and former smokers
AU - Lee, J. Jack
AU - Liu, Diane
AU - Lee, Jin Soo
AU - Kurie, Jonathan M.
AU - Khuri, Fadlo R.
AU - Ibarguen, Heladio
AU - Morice, Rodolfo C.
AU - Walsh, Garrett
AU - Ro, Jae Y.
AU - Broxson, Anita
AU - Hong, Waun Ki
AU - Hittelman, Walter N.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2001/7/18
Y1 - 2001/7/18
N2 - Background: Lung cancer risk remains elevated for many years after quitting smoking. To assess using proliferation indices in bronchial tissues as an intermediate endpoint biomarker in lung cancer chemoprevention trials, we determined the relationship between the extent, intensity, and cessation of tobacco smoking and proliferative changes in bronchial epithelial biopsy specimens. Methods: Bronchial biopsy specimens were obtained from up to six epithelial sites in 120 current smokers (median pack-years, 42) and 207 former smokers (median pack-years, 40; median quit-years, 8.1). Sections from the paraffin-embedded specimens were stained with hematoxylin-eosin to determine the metaplasia index and with an antibody to Ki-67 to determine the proliferative (labeling) index for the basal and parabasal (Ki-67 PLI) layers. All statistical tests were two-sided. Results: Biopsy sites with metaplasia had statistically significantly higher Ki-67-labeling indices than those without metaplasia (P<.001) in both current and former smokers. Increased proliferation was observed in multiple biopsy sites, with the average Ki-67 PLI of the subject strongly correlating with the metaplasia index (r = .72 for current smokers; P<.001), even in sites without metaplasia (r = .23 for current smokers; P<.001). In current smokers, the Ki-67 PLI was associated with the number of packs smoked/day (P = .02) but not with smoking years or pack-years. In subjects who had quit smoking, the Ki-67 PLI dropped statistically significantly within 1 year (P = .008) but remained detectable for more than 20 years, even in the absence of squamous metaplasia. Conclusion: Smoking appears to elicit a dose-related proliferative response in the bronchial epithelia of active smokers. Although the proliferative response decreased gradually in former smokers, a subset of individuals had detectable proliferation for many years and may benefit from targeted chemoprevention. Bronchial epithelial proliferation, measured by Ki-67, may provide a useful biomarker in the assessment of lung cancer risk and in the response to chemopreventive interventions.
AB - Background: Lung cancer risk remains elevated for many years after quitting smoking. To assess using proliferation indices in bronchial tissues as an intermediate endpoint biomarker in lung cancer chemoprevention trials, we determined the relationship between the extent, intensity, and cessation of tobacco smoking and proliferative changes in bronchial epithelial biopsy specimens. Methods: Bronchial biopsy specimens were obtained from up to six epithelial sites in 120 current smokers (median pack-years, 42) and 207 former smokers (median pack-years, 40; median quit-years, 8.1). Sections from the paraffin-embedded specimens were stained with hematoxylin-eosin to determine the metaplasia index and with an antibody to Ki-67 to determine the proliferative (labeling) index for the basal and parabasal (Ki-67 PLI) layers. All statistical tests were two-sided. Results: Biopsy sites with metaplasia had statistically significantly higher Ki-67-labeling indices than those without metaplasia (P<.001) in both current and former smokers. Increased proliferation was observed in multiple biopsy sites, with the average Ki-67 PLI of the subject strongly correlating with the metaplasia index (r = .72 for current smokers; P<.001), even in sites without metaplasia (r = .23 for current smokers; P<.001). In current smokers, the Ki-67 PLI was associated with the number of packs smoked/day (P = .02) but not with smoking years or pack-years. In subjects who had quit smoking, the Ki-67 PLI dropped statistically significantly within 1 year (P = .008) but remained detectable for more than 20 years, even in the absence of squamous metaplasia. Conclusion: Smoking appears to elicit a dose-related proliferative response in the bronchial epithelia of active smokers. Although the proliferative response decreased gradually in former smokers, a subset of individuals had detectable proliferation for many years and may benefit from targeted chemoprevention. Bronchial epithelial proliferation, measured by Ki-67, may provide a useful biomarker in the assessment of lung cancer risk and in the response to chemopreventive interventions.
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U2 - 10.1093/jnci/93.14.1081
DO - 10.1093/jnci/93.14.1081
M3 - Article
C2 - 11459869
AN - SCOPUS:0035908486
VL - 93
SP - 1081
EP - 1088
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
SN - 0027-8874
IS - 14
ER -