Expression of cyclooxygenase-1 and cyclooxygenase-2 in bronchial epithelium and nonsmall cell lung carcinoma
Expression of cyclooxygenase-1 and cyclooxygenase-2 in bronchial epithelium and nonsmall cell lung carcinoma
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作者：
Hast端rk, S;Kemp, B;Lee, JS
背景：环氧合酶（Cyclooxygenase，考克斯）是非甾体类抗肿瘤药物的主要靶酶，在实验模型和流行病学研究中均显示其抑制肿瘤发生。为了评估其作为支气管化学预防试验中中间生物标志物的实用性，作者使用免疫组织化学染色技术检测了正常和癌前支气管上皮细胞和非小细胞肺癌（NSCLC）样本中的考克斯1和考克斯2表达。本研究包括101例NSCLC样本和77例支气管活检样本，均来自15名健康吸烟者。在正常支气管上皮中，发现考克斯2表达完全阴性，而考克斯I表达在少数散在细胞中被注意到。基底细胞增生和鳞状上皮化生的区域表现出相同的模式。与考克斯1阳性肿瘤相比，考克斯2阳性肿瘤（通过> 10%的肿瘤细胞中的阳性染色来定义）相对较多（101个肿瘤中的30个[30%] vs. 101个肿瘤中的14个[14%]; P = 0.01）。当考虑肿瘤类型时，与鳞状细胞癌相比，有更多的考克斯2阳性腺癌（51例腺癌中的21例[41%] vs. 46例鳞状细胞癌中的9例[20%]; P = 0.03）。相比之下，与鳞状细胞癌相比，更少的腺癌倾向于显示考克斯1表达（51例腺癌中的4例[8%] vs 46例鳞状细胞癌中的9例[20%]; P = 0.14）。尽管吸烟者的考克斯2阳性肿瘤多于非吸烟者（吸烟者91个肿瘤中有29个[32%] vs.非吸烟者10个肿瘤中有1个[10%]; P = 0.15），但在考克斯I或考克斯2表达与吸烟状态或有统计学意义的临床病理特征之间没有发现统计学意义的关系。目前的研究结果表明，考克斯I和考克斯2的表达可能不是一个有用的中间生物标志物在支气管化学预防试验。然而，考虑到肿瘤细胞中考克斯I和考克斯2表达的模式，当为NSCLC患者的子集设计治疗策略时，考克斯表达状态可能是有用的参数。(C)2002年美国癌症协会。
BACKGROUND, Cyclooxygenase (Cox) is the main target enzyme for the nonsteroidal antiinflammatory drugs that have been shown to suppress carcinogenesis in both experimental models and epidemiologic studies.METHODS. To evaluate its utility as an intermediate biomarker in bronchial chemoprevention trials, the authors examined Cox 1 and Cox 2 expression in normal and premalignant bronchial epithelial cells and nonsmall cell lung carcinoma (NSCLC) samples using an immunohistochemical staining technique. Included in the current study were 101 NSCLC samples and 77 bronchial biopsy samples obtained from 15 healthy smokers.RESULTS. In the normal bronchial epithelium, Cox 2 expression was found to be completely negative whereas Cox I expression was noted in a few scattered cells. The areas of basal cell hyperplasia and squamous metaplasia demonstrated the same pattern. There were relatively more Cox 2-positive tumors, as defined by positive staining in > 10% of tumor cells, than Cox 1-positive tumors (30 of 101 tumors [30%] vs. 14 of 101 tumors [14%]; P = 0.01). When tumor types were considered, there were more Cox 2-positive adenocarcinomas compared with squamous cell carcinomas (21 of 51 adenocarcinomas [41%] vs. 9 of 46 squamous cell carcinomas [20%]; P = 0.03). In contrast, fewer adenocarcinomas tended to show Cox 1 expression compared with squamous cell carcinomas (4 of 51 adenocarcinomas [8%] vs. 9 of 46 squamous cell carcinomas [20%]; P = 0.14). Although smokers tended to have more Cox 2-positive tumors than nonsmokers (29 of 91 tumors in the smokers [32%] vs. I of 10 tumors in the nonsmokers [10%]; P = 0.15), there was no statistically significant relation found between Cox I or Cox 2 expression and smoking status or prognostically significant clinicopathologic features.CONCLUSIONS. The results of the current study suggest that Cox I and Cox 2 expression may not be a useful intermediate biomarker in bronchial chemoprevention trials. Nevertheless, considering the patterns of Cox I and Cox 2 expression in tumor cells, Cox expression status may be a useful parameter when designing treatment strategies for a subset of NSCLC patients. (C) 2002 American Cancer Society.