Kennedy T C, Proudfoot S P, Franklin W A, Merrick T A, Saccomanno G, Corkill M E, Mumma D L, Sirgi K E, Miller Y E, Archer P G, Prochazka A
Lung Cancer Institute of Colorado, Denver 80218, USA.
Cancer Res. 1996 Oct 15;56(20):4673-8.
Advances in the understanding of lung cancer biology have led to observations that specific genetic changes occur in premalignant dysplasia. These observations have occurred predominantly in molecular studies of resected lung tumors and consequently, they may not be fully representative of those biological abnormalities characterizing premalignant lesions in individuals without overt lung cancer. Studies of premalignant epithelial cell biology and chemoprevention are needed in this patient subgroup. Such an initiative is now underway through the lung cancer Specialized Program of Research Excellence (SPORE) grant awarded to the University of Colorado Cancer Center (and affiliated institutions) by the National Cancer Institute. To identify participants for the early detection and chemoprevention trials of the Colorado SPORE, we initiated a sputum cytology screening program targeting persons with chronic obstructive pulmonary disease and smoking histories of 40 or more pack-years. During the first 26 months after activation of the screening program, sputum samples from 632 participants were evaluated. Of these, 533 (84%) of the subjects submitted specimens deemed adequate for cytopathological interpretation; 99 (16%) provided sputum samples unsuitable for cytodiagnosis. Of those participants who submitted adequate samples, 48% had cytodiagnoses of mild dysplasia, 26 % had moderate to severe dysplasia, and 2% presented with carcinoma in situ or invasive carcinoma. Logistic regression modeling was pursued to determine whether selected demographic and/or clinical status variables could be identified as statistically significant predictors of the specific cytological outcome to be expected (mild dysplasia, moderate dysplasia, and so forth). The only apparent associations found from both univariate and multivariate analyses were that the total number of pack-years of smoking history decreased with severity of cytodiagnosis and that those individuals with mild or moderate dysplasia were more likely to be ex-smokers than those with grades of regular metaplasia or lower. Based on the initial results of the Colorado SPORE sputum cytology screening program, we conclude that persons with chronic obstructive pulmonary disease and 40 or more pack-years of smoking history have a high prevalence of premalignant dysplasia detectable through sputum cytology and should be targeted for research programs focusing on lung cancer prevention, early detection, and exploratory biomarker studies.
对肺癌生物学认识的进展引发了一些观察结果，即特定的基因变化发生在癌前发育异常中。这些观察结果主要出现在对切除的肺肿瘤的分子研究中，因此，它们可能无法完全代表那些表征无明显肺癌个体癌前病变的生物学异常。在这个患者亚组中，需要对癌前上皮细胞生物学和化学预防进行研究。通过美国国立癌症研究所授予科罗拉多大学癌症中心（及附属机构）的肺癌卓越专项研究计划（SPORE）资助，目前正在开展这样一项倡议。为了确定科罗拉多SPORE早期检测和化学预防试验的参与者，我们启动了一项痰细胞学筛查计划，目标人群为患有慢性阻塞性肺疾病且吸烟史达40包年或以上的人。在筛查计划启动后的前26个月里，对632名参与者的痰样本进行了评估。其中，533名（84%）受试者提交的样本被认为适合进行细胞病理学解读；99名（16%）提供的痰样本不适合进行细胞诊断。在提交了合适样本的参与者中，48%的细胞诊断为轻度发育异常，26%为中度至重度发育异常，2%为原位癌或浸润癌。采用逻辑回归模型来确定是否可以将选定的人口统计学和/或临床状态变量确定为预期特定细胞学结果（轻度发育异常、中度发育异常等）的统计学显著预测因素。单变量和多变量分析中唯一明显的关联是，吸烟史的总包年数随细胞诊断的严重程度而减少，并且轻度或中度发育异常的个体比具有正常化生等级或更低等级的个体更有可能是戒烟者。基于科罗拉多SPORE痰细胞学筛查计划的初步结果，我们得出结论，患有慢性阻塞性肺疾病且吸烟史达40包年或以上的人通过痰细胞学检测出癌前发育异常的患病率很高，应作为肺癌预防、早期检测和探索性生物标志物研究的重点研究对象。
