Long-term impact of smoking on lung epithelial proliferation in current and former smokers
Long-term impact of smoking on lung epithelial proliferation in current and former smokers
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DOI：
10.1093/jnci/93.14.1081
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发表时间：
2001-07-18
期刊：
影响因子：
--
通讯作者：
Hittelman, WN
中科院分区：
文献类型：
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作者：
Lee, JJ;Liu, D;Hittelman, WN
背景：戒烟多年后，肺癌风险仍然很高。为了评估在肺癌化学预防试验中使用支气管组织的增殖指数作为中间终点生物标志物，我们确定了吸烟的程度、强度和戒烟与支气管上皮活检标本的增殖变化之间的关系。方法：从120名当前吸烟者(中位数为42岁)和207名既往吸烟者(中位数为40岁；石蜡包埋标本切片苏木精-伊红染色以确定化生指数，并用Ki-67抗体测定基底层和旁基底层(Ki-67 PLI)的增殖指数。结果：无论是现在吸烟者还是既往吸烟者，有化生的活检部位Ki-67标记指数均显著高于无化生的活检部位(P<；.001)。在多个活检部位观察到增殖增加，受试者的平均Ki-67 PLI与化生指数强烈相关(对于当前吸烟者，r=.72；P<；.001)，即使在没有化生的部位(对于当前吸烟者，r=.23；P<；在当前吸烟者中，Ki-67 PLI与每天吸烟的香烟数量相关(P=0.02)，而与吸烟年限或吸烟年限无关。在戒烟者中，Ki-67 PLI在1年内显著下降(P=.008)，但在20多年后仍可检测到，即使在没有鳞状上皮化生的情况下也是如此。结论：吸烟似乎在活跃吸烟者的支气管上皮中引发了与剂量相关的增殖反应。尽管以前吸烟者的增殖反应逐渐降低，但有一部分人多年来一直有可检测到的增殖，并可能受益于有针对性的化学预防，通过Ki-67测量的支气管上皮增殖可能在评估肺癌风险和对化学预防干预的反应中提供有用的生物标志物。
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.