Laga Alvaro C, Zander Dani S, Cagle Philip T
Department of Pathology, Baylor College of Medicine, Houston, TX, USA.
Arch Pathol Lab Med. 2005 Sep;129(9):1113-7. doi: 10.5858/2005-129-1113-PSOCEI.
Previous studies report that increased expression of cyclooxygenase 2 (COX-2) correlates with poor clinical outcome in several malignancies, including non- small cell lung carcinoma (NSCLC). Cyclooxygenase 2 inhibitors have been reported to effectively inhibit carcinogenesis in colon cancer experimental models.
We examined COX-2 expression in 259 cases of NSCLC to evaluate its prognostic significance.
Sections of NSCLC from patients with a median 5-year follow-up were immunostained with COX-2 monoclonal antibody (1:150) using the Dako mouse EnVision;pl system. Extent of COX-2 expression in neoplastic cells was recorded as follows: 0, 0% to 10% of cells positive; 1, 11% to 33% positive; 2, 34% to 66% positive; and 3, more than 66% positive. Intensity was scored as either increased (+) or not increased (-), compared to internal control smooth muscle and endothelial cells. Kaplan-Meier analysis was used to assess the relationship between survival and COX-2 expression, using the log-rank test for statistical significance.
No relationship was found between the extent and/or the intensity of COX-2 expression and patient survival when the entire cohort was considered. However, when separately analyzed according to disease stage and intensity of COX-2 expression, a significant relationship (P = .03) between increased COX-2 expression and shortened patient survival was found only in patients with stage I and II NSCLC.
To our knowledge, this is the largest series of NSCLCs in which COX-2 has been investigated as a prognostic marker. The findings in this large series support previous studies of smaller cohorts that reported that increased COX-2 expression predicts poor outcome in patients with early-stage NSCLC.
既往研究报道,环氧化酶2(COX-2)表达增加与包括非小细胞肺癌(NSCLC)在内的多种恶性肿瘤的不良临床结局相关。据报道,环氧化酶2抑制剂在结肠癌实验模型中可有效抑制肿瘤发生。
我们检测了259例NSCLC患者的COX-2表达,以评估其预后意义。
使用Dako小鼠EnVision;pl系统,用COX-2单克隆抗体(1:150)对中位随访时间为5年的NSCLC患者的切片进行免疫染色。肿瘤细胞中COX-2表达程度记录如下:0,0%至10%的细胞阳性;1,11%至33%阳性;2,34%至66%阳性;3,超过66%阳性。与内部对照平滑肌和内皮细胞相比,强度评分为增加(+)或未增加(-)。采用Kaplan-Meier分析评估生存与COX-2表达之间的关系,使用对数秩检验进行统计学显著性分析。
当考虑整个队列时,未发现COX-2表达程度和/或强度与患者生存之间存在相关性。然而,根据疾病分期和COX-2表达强度进行单独分析时,仅在I期和II期NSCLC患者中发现COX-2表达增加与患者生存缩短之间存在显著相关性(P = 0.03)。
据我们所知,这是研究COX-2作为预后标志物的最大系列NSCLC研究。这个大系列的研究结果支持了之前对较小队列的研究,即COX-2表达增加预示早期NSCLC患者预后不良。